Topographic analysis of Horner's syndrome

Horner's syndrome or oculosympathetic paralysis is not an uncommon finding in patients with head and neck neoplasms. While in most cases the syndrome is easily established at the bedside, it can be confirmed and topographically defined as a central, preganglionic, or postganglionic lesion through sequential pharmacologic testing. The importance of such localization lies in differentiating neoplasia vs. a benign condition as the cause of the syndrome. Such variants as congenital Horner's, an alternating Horner's, and a pseudo-Horner's syndrome are discussed in regard to their differential features.     

Bumpy muscles

A 63-year-old man developed bilateral conjunctival injection and irritation followed by periocular discomfort and diplopia. Within weeks left proptosis and intermittent fever were noted. Orbital CT scan showed bilateral nodular enlargement of multiple extraocular muscles. Fine needle aspiration biopsy of the extraocular muscles revealed neoplastic cells compatible with a renal cell carcinoma. The bilateral extraocular muscle metastases were the initial manifestations of the underlying malignancy.     

Optic neuropathy and central nervous system disease secondary to Sj?gren's syndrome in a child

The authors describe a 10-year-old girl in whom optic neuropathy and central nervous system (CNS) disease developed in association with primary Sj?gren's syndrome. There was angiographic evidence of cerebral vasculitis and multiple infarcts present on neuroimaging. Results of parotid biopsy, cerebrospinal fluid, and serologic analyses showed abnormalities that were consistent with the diagnosis of Sj?gren's syndrome. Although the patient had optic disc pallor on initial evaluation, her color vision and acuity improved with immunosuppressive therapy, as did her other neurologic symptoms. The authors believe this represents the first reported case of optic neuropathy and CNS disease associated with primary Sj?gren's syndrome in the pediatric population. The possibility of improvement in visual function with early institution of immunosuppressive therapy makes prompt diagnosis essential.     

Lack of effect of opioid peptides,morphine and naloxone on superoxide formation in human neutrophils and HL-60 leukemic cells

Summary There are controversial reports in the literature concerning the effects of opioids on superoxide (O ₂ ^– ) formation in phagocytes, these agents being either inhibitory or stimulatory. We re-examined this issue and compared the effects of the Chemotactic peptide, N-formyl-l,-methionyl-l-leucyl-l-phenylalanine (fMet-Leu-Phe), phorbol myristate acetate (PMA), ATP, platelet activating factor (PAF), cytochalasin B (CB) and prostaglandin E₁ (PGE₁) with those of various opioids on O ₂ ^– formation in human neutrophils and HL-60 leukemic cells under defined experimental conditions. In the presence of CB, fMet-Leu-Phe and PAF concentration-dependently activated O ₂ ^– formation in neutrophils with EC₅₀ values of 20 nM and 100 nM, respectively. In the absence of CB, fMet-Leu-Phe and PAF were much less effective. PAF synergistically enhanced O ₂ ^– formation induced by fMet-Leu-Phe. ATP at a concentration of 100 M and the opioids, methionine enkephalin, -endorphin, dynorphin, [d-Ala², N-Me-Phe⁴, Gly⁵-ol]-enkephalin, [d-Ala²-d-Leu⁵]-enkephalin and morphine at concentrations between 10 pM to 1 M did not activate O ₂ ^– formation. ATP but not \-endorphin potentiated fMet-Leu-Phe-induced O ₂ ^– formation. O ₂ ^– formation induced by a maximally stimulatory concentration of PMA (100 ng/ml) was enhanced by fMet-Leu-Phe but was unaffected by methionine enkephalin or PGE₁. PMA at a non-stimulatory concentration (2 ng/ml) potentiated the effect of fMet-Leu-Phe but did not induce responsiveness to PAF, ATP or -endorphin. PGE₁ strongly inhibited fMet-Leu-Phe-induced O ₂ ^– formation, whereas morphine, methionine enkephalin and the opioid antagonist, naloxone, were without effect. In HL-60 cells differentiated with dibutyryl cAMP, fMet-Leu-Phe, PAF and ATP but not -endorphin activated O ₂ ^– formation. Our results show that O ₂ ^– formation is differentially regulated by various classes of intercellular signal molecules and that opioids do not play a role in the regulation of O ₂ ^– formation. The precise definition of the experimental conditions and control experiments with established modulators of O ₂ ^– formation are essential to evaluate the role of opioids in the regulation of this effector system.Send offprint requests to R. Seifert at the above address     

Accumulation of p53 in response to adenovirus early region 1A sensitizes human cells to tumor necrosis factor alpha-induced apoptosis

Many tumor cells are resistant to tumor necrosis factor alpha (TNFalpha)-induced apoptosis. Adenovirus early region 1A (AdE1A) sensitizes the otherwise resistant cells to TNFalpha. AdE1A also stabilizes the p53 protein. The present study demonstrates a correlation between AdE1A-induced sensitization and stabilization of p53 in TNFalpha-induced apoptosis since the N-terminal and CR2 regions, the binding sites for CBP/p300, Rb and 26S proteasome regulatory components, are required for both these actions of AdE1A. TNFalpha does not induce apoptosis and AdE1A fails to sensitize TNFalpha cytotoxicity in p53-negative cells. However, introduction of exogenous p53 overcomes the cellular resistance to TNFalpha toxicity and enhances AdE1A sensitization, demonstrating that AdE1A sensitizes TNFalpha-induced apoptosis by its stabilization of p53. A proteasome inhibitor, lactacystin, enhances TNFalpha cytotoxicity in p53-positive and -negative cells, suggesting that accumulation of cellular proteins other than p53 might also regulate the cellular response to TNFalpha signaling.     

Cationic-amphiphilic arpromidine-derived guanidines and a histamine trifluoromethyl-toluidide derivative may activate pertussis toxin-sensitive G-proteins by a receptor-independent mechanism

Formyl peptides activate superoxide anion (O₂ ^–) formation in human neutrophils and in HL-60 cells via pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins), and histamine (HA) mediates inhibition of O₂ ^– formation via H₂-receptors. We have studied the effects of lipophilic arpromidine-derived guanidines, which are potent, full H₂-receptor agonists in the guinea pig atrium, on O₂ ^– formation and on activation of G-proteins in HL-60 membranes and on purified G-proteins. We have also studied the effects of a HA trifluoromethyl-toluidide derivative (HTMT), a cationic-amphiphilic HA derivative which activates O₂ ^– formation in HL-60 cells through a mechanism which is independent of known HA receptor subtypes, on G-protein activation. Guanidines, at concentrations, up to 30 mol/l inhibited and, at concentrations above 30 mol/l, enhanced formyl peptide-induce O₂ ^– formation in neutrophils. In HL-60 cells, guanidines per se activated O₂ ^– formation. The stimulatory effects of guanidines on O₂ ^– formation were not inhibited by H₁- or H₂-receptor antagonists. In HL-60 membranes, guanidines and HTMT, activated high-affinity GTPase in a PTX-sensitive manner. These substances also increased GTP hydrolysis effected by transducin and G_i/G_o-proteins. Our data suggest that lipophilic guanidines and HTMT may act as receptor-independent activators of PTX-sensitive G-proteins, resulting in stimulation of O ₂ ^– formation.     

Elevated levels of the antimicrobial peptide LL‐37 in hidradenitis suppurativa are associated with a Th1/Th17 immune response

Hidradenitis suppurativa (HS) is an inflammatory skin disease with poorly understood immunopathogenic mechanisms. LL‐37 is an antimicrobial peptide, which is transcribed from the CAMP (cathelicidin antimicrobial peptide) gene. Previous reports showed upregulated levels of CAMP and LL‐37 in HS lesions, and therefore, the aim of this study was to compare levels of LL‐37 in HS to other inflammatory skin diseases and to establish immunomodulatory functions of LL‐37 in HS. We confirm an upregulation of the LL‐37 peptide in lesional HS skin with comparable levels as in psoriasis patients and are able to positively correlate the presence of LL‐37 in HS with the presence of T cells, macrophages, neutrophils, IFN‐γ, IL‐17, IL‐23, TNF‐α, IL‐32 and IL‐1β. Mechanistically, LL‐37 boosts the proliferation of unspecifically activated CD4⁺ T cells via an increased calcium signalling independent of antigen‐presenting cells. Targeting LL‐37 may therefore represent a new therapeutic option for the treatment of this recalcitrant disease, but it has to be kept in mind that LL‐37 also has an antimicrobial function.