Quinine-dependent antibodies to neutrophils react with a 60-Kd glycoprotein on which neutrophil-specific antigen NB1 is located and an 85-Kd glycosyl-phosphatidylinositol-linked N-glycosylated plasma membrane glycoprotein

We have previously described a 24-year-old woman with quinine-dependent antibodies that reacted with neutrophils, red blood cells (RBCs), platelets, and T lymphocytes. The drug-dependent neutrophil antibody was found to react with 85- and 60-Kd neutrophil membrane molecules. In these studies, we further characterized these molecules and found that both were glycosyl-phosphatidylinositol (GPI)-linked and contained sialic acid residues and N-linked carbohydrate side chains, but neither contained O-linked carbohydrates. The protein backbone of the 60-Kd molecule was 45 Kd, and the 85 Kd glycoprotein (GP) was made up of 33- and 31-Kd proteins. While some GPI-anchored neutrophil GPs are released by stimulated neutrophils, neither the 85- nor the 60-Kd GP was released by neutrophil stimulated with C5a, f-met-leu-phe (FMLP), or phorbol myristate acetate (PMA). Neutrophil-specific antigen NB1 is located on a 58- to 64-Kd GP. To determine if the quinine-dependent antibody and anti-NB1 recognize the same GP, immunoprecipitation studies were performed with the quinine-dependent antibody using neutrophils with varying NB1 phenotypes. The 60-Kd GP was detected on NB1-positive neutrophils from 11 of 12 donors tested, but not on NB1- negative neutrophils from two donors tested. After solubilized 125I- labeled neutrophils were absorbed with anti-NB1, the quinine-dependent antibody immunoprecipitated the 85-Kd GP, but not the 60-Kd GP. These results indicate that anti-NB1 and the quinine-dependent antibody identified the same GP. The 85-Kd GP was detected on neutrophils from all 14 donors tested. The electrophoretic mobility of the 85-Kd GP was similar to the electrophoretic mobility of the major 125I-labeled neutrophil protein.     

Hydroxyurea increases fetal hemoglobin in cultured erythroid cells derived from normal individuals and patients with sickle cell anemia or beta-thalassemia

Hydroxyurea (HU), an inhibitor of DNA synthesis, has been shown to increase fetal hemoglobin (HbF) levels in patients with sickle cell anemia and in some patients with beta-thalassemia. However, until now there have not been good in vitro model systems that simulate this effect for study of the molecular and cellular mechanism(s) involved in perturbing the normal ontogeny of the globin genes. We analyzed the cellular effects of HU using a two-phase liquid culture procedure (Fibach et al: Blood 73:100, 1989) in which human peripheral blood- derived progenitor cells undergo proliferation and differentiation. HU was found to have multiple effects on these cultured cells: (1) an increase in the proportion of HbF produced; (2) a decrease in cell number due to inhibition of cell proliferation; (3) an increase in hemoglobin content per cell (mean corpuscular hemoglobin [MCH]); and (4) an increase in cell size (mean corpuscular volume). The extent of these effects was related to the HU dose and time of addition. When added to cell cultures from normal individuals, 4 days following their exposure to erythropoietin (EPO), 100 mumol/L HU caused a 1.3- to 3.5- fold increase in the proportion of HbF, from 0.4% to 5.2% (mean 1.6) in untreated to 1.5% to 8.2% (mean 3.1) in HU-treated cultures and a 45% +/- 10% increase in MCH but only a 25% +/- 7% decrease in cell number on day 13. Cultures of cells derived from five patients with sickle cell anemia have shown a twofold to fivefold increase in the percentage of Hb F following addition of HU while four patients with beta- thalassemia showed a 1.3- to 6.2-fold increase. We believe that this primary cell culture procedure should prove useful in studying the cellular and molecular mechanisms of pharmacologic induction of HbF and might provide a valuable predictive assay system for evaluation of the response of individual patients with hemoglobinopathies to HU and similar agents.     

The additive value of second opinion teleconsulting in the management of patients with challenging inflammatory,neoplastic skin diseases: a best practice model in dermatology?

BACKGROUND: Telemedicine is the practice of healthcare using interactive processes of communication to facilitate healthcare delivery, including diagnosis, consultation and treatment, as well as education and transfer of medical data. The aim of teledermatology, just as telemedicine, is to promote best practice procedures and to improve the consistency and competence of health care. AIM: To investigate the diagnostic additive value of second opinion teleconsulting in patients with challenging dermatoses, among dermatologists working in two different dermatology departments. SETTING: Thirty-three cases of patients with challenging inflammatory and neoplastic skin diseases at the University of L'Aquila Department of Dermatology were sent for teleconsultation to the Department of Dermatology, Medical University of Graz, Austria. METHODS: All cases were selected in the outpatient service in L'Aquila. After face-to-face consultation with a local colleague had been completed, images were sent using a store-and-forward (SAF)-based system (http://www.telederm.org) to Graz. Histopathological examination together with follow-up of the patient represents the diagnostic gold standard for this study. RESULTS: Telediagnosis was correct in 26 of 33 (78.8%) cases. Sixteen of 33 cases (48.5%) had already been diagnosed face-to-face by at least one of the two dermatologists in L'Aquila. In 10 of 33 cases (30.3%), the correct diagnosis was made in teleconsultation only. CONCLUSIONS: Second opinion teleconsulting may represent an additive value in the diagnosis of numerous challenging inflammatory and neoplastic skin diseases. It may be particularly useful as a best practice model for smaller departments in order to discuss and/or to confirm diagnoses and also for the management of patients with unusual difficult dermatoses.     

Plasma cell mucositis

A case of plasma cell mucositis is described for its rarity. A probable aetiological correlation with periodontitis is discussed. The patient showed good response to intralesional and topical steroids.     

1-Deprenyl test in migraine: neuroendocrinological aspects

We evaluated the effect of 1-deprenyl, a drug that increases the availability of endogenous dopamine, on the plasma levels of prolactin and growth hormone in 10 female patients with migraine and in 10 control subjects matched for age and menstrual phase. The patients showed a significant decrease in prolactin levels at 30, 60 and 120 min after the oral administration of 5 mg of 1-deprenyl when compared with the values obtained in controls ( p < 0.001). The effects of 1-deprenyl on growth hormone plasma levels were not significantly different between patients and controls. These data suggest that 1-deprenyl inhibits prolactin release in migraine patients, but not in control subjects. This differential sensitivity could be explained by dopamine receptor supersensitivity in migraine patients.