Bullous pemphigoid in association with cutaneous lesions specific to a myelodysplastic syndrome

Specific cutaneous lesions are a rare occurrence in myelodysplastic syndromes (MDS). The concurrent association of blistering skin lesions similar to those in bullous pemphigoid (BP), even though a rare event, suggests that BP may be a paraneoplastic syndrome. We report an 86-year-old man who had a refractory anaemia with excess bone marrow blasts in transformation, who developed a generalized pruritic blistering eruption. Immunohistopathological tests showed subepidermal blisters with linear deposits of IgG and C3 along the basement membrane zone of the epidermis surrounding a tumoral dermal infiltrate of CD13+ and CD15+ cells. Immunoblotting studies using epidermal extracts revealed circulating IgG antibodies against three protein bands: a 210–215 kDa band. a 180kDa band which co-migrated with the BP 180 antigen, and a 190kDa band. The tumour infiltrate may have revealed antigenic determinants which led to the onset of BP. The concept of paraneoplastic pemphigoid remains to be either confirmed or invalidated by further epidemiological studies.     

Comparison of the photochemical behavior of four different photoactivatable probes

The most commonly used photoaffinity labeling probes are compared, which are aryl azides, aryl diazirines, α-diazocarbonyls and benzophenone-derivatives. The compounds were used under identical conditions and crosslinking efficiency, influence of water, irradiation requirements, and by-products were investigated. Using the pentapeptide thymopentin (TP5) as a model system, we synthesized four analogues by solid-phase peptide synthesis and partially N-terminal modification to obtain [p-(3-trifluoromethyl)diazirinophenylalanine⁵] TP5, [p-benzoylphenylalanine⁵] TP5, 4-azidobenzoyl-TP5 and 2-diazo-3, 3, 3-trifluoropropionyl-TP5. The peptides were characterized by HPLC and ion-spray mass spectroscopy. Irradiation of the peptides with two different ultraviolet sources was carried out in water, n-propanol and water/n-propanol to imitate both hydrophobic and hydrophilic peptide/protein-interactions as well as the influence of the aqueous environment. Analysis of the products with HPLC, ion-spray MS, HPLC-MS and HPLC-CID-MS revealed that (Tmd)Phe is a highly potent carbene-precursor, which can be transformed easily into uniform crosslinking products by smooth photolysis. However, the electrophilic nature of the intermediate causes a high tendency to react with water molecules. The 4-azidobenzoyl group showed comparable crosslinking efficiency, but the probability to create non-uniform irradiation products (e.g. through rearrangement) is higher, whereas the reaction with water is less dominant. In contrast, Bpa was found to have an extremely low affinity to react with water, whereas prolonged UV irradiation is needed to get complete rearrangement into a variety of products. As the absorption band of α-diazocarbonyls at around 350 nm possesses a low extinction coefficient, 2-diazo-3, 3, 3-trifluoropropionyl-TP5 could not be activated at all with the optimized irradiation conditions that we have chosen for our comparative studies. © Munksgaard 1997.     

ACEA-1328, AN NMDA RECEPTOR ANTAGONIST, INCREASES THE POTENCY OF MORPHINE AND U50,488H IN THE TAIL FLICK TEST IN MICE

The effect of 5-nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328), a competitive and systemically bioavailable NMDA receptor/glycine site antagonist, was examined on opioid-induced antinociception in the tail flick test. Swiss Webster mice were injected with ACEA-1328 either alone or in combination with morphine or (±)-trans-U-50488 methanesulfonate (U50,488H), a μ- and a κ-opioid receptor agonist, respectively, and tested for antinociception. Systemic administration of ACEA-1328 alone increased the tail flick latencies with an ED₅₀of approximately 45 mg kg⁻¹. Concurrent administration of ACEA-1328 with morphine, or U50,488H, at doses that did not affect tail flick latencies, potentiated the antinociceptive effect of the opioid analgesics and vice versa. Naloxone, an opioid receptor antagonist, while not modifying the effect of ACEA-1328, did block the augmentation, suggesting that opioid receptors might be involved in the latter effect. 5-Aza-7-chloro-4-hydroxy-3-(m-phenoxyphenyl)quinoline-2(1H)-one (ACEA-0762), a selective NMDA receptor/glycine site antagonist, also showed enhancement of the antinociceptive effect of morphine and U50,488H. However, concurrent administration of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX), a selective non-NMDA receptor antagonist, with morphine did not alter the antinociceptive potency of the opioid analgesic. Overall, the data suggest that ACEA-1328 may increase the potency of the opioid analgesics by antagonising the glycine site associated with the NMDA receptor.     

Nifedipine and alpha1-adrenergic blockade in Raynaud's phenomenon

The efficacy of nifedipine and prazosin in the treatment ofRaynaud's phenomenon was assessed in a prospective double-blindrandomized cross-over trial in 15 patients. Each patient receivedone week of nifedipine 20 mg TID, one week of prazosin 1 mgTID, and 2 weeks of placebo. Nifedipine was shown to be effectivein reducing both the frequency and the severity of Raynaud'sphenomenon, whereas prazosin was ineffective. Before initiationof therapy in the 15 patients, pressor responses to the intravenousalpha₁-agonist phenylephrine were assessed in the basal state,30 min after 20 mg oral nifedipine, and 30 min after 1 mg oralprazosin; the shift to the right of the log dose-vasopressorresponse curves to phenylephrine was similar with nifedipineand prazosin.     

PREDICTION OF PERMANENT WORK DISABILITY IN A FOLLOW-UP STUDY OF EARLY RHEUMATOID ARTHRITIS: RESULTS OF A TREE STRUCTURED ANALYSIS USING RECPAM

The objectives of this study are: (a) to determine the occurrenceof permanent work disability (PWD) in early rheumatoid arthritis(RA); (b) to identify prognostic groups of patients; (c) toassess the employment rates for these groups over time. Seventy-threegainfully employed consecutive out-patients with early RA (     

'Original antigenic sin', T cell memory, and malaria sporozoite immunity: an hypothesis for immune evasion

Prior to any exposure to malaria, most adults have T cells specific for malaria parasites and various malaria proteins. The protein for which this has been shown more than any other is the circumsporozoite protein (CSP) of Plasmo-dium falciparum. These T cells can be present in high frequency and appear to have arisen through exposure to other (non-malaria) organisms. Although T cells are thought to provide protection against sporozoites, these T cells specific for cross-reactive organisms are clearly unable to protect against malaria, and may be preferentially expanded following exposure to malaria sporozoites. Thus, cross-reactive organisms have the potential to skew the repertoire of sporozoite-induced T cells and affect the induction of protective immunity. This is analogous to the concept of 'original antigenic sin' whereby prior exposure to one strain of influenza virus was shown to be able to divert the antibody response to a second challenging strain to focus on the shared (cross-reactive) epitopes.