bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutaneous sclerosing perineurioma of the digits: an uncommon soft‐tissue neoplasm. Report of two cases with immunohistochemical analysis
Authors: Canales‐Ibarra Claudia , Magariños Gabriel , Olsoff‐Pagovich Paul , Ortiz‐Hidalgo Carlos 
Published: September 2003

Background:  Cutaneous sclerosing perineurioma is a recently characterized, uncommon tumor composed of perineurial cells, which exhibits immunoreactivity for epithelial membrane antigen (EMA). These lesions occur preferentially in children and young adults and usually develop as dermal or subcutaneous nodules in the hands or palms.Methods:  We report two cases of cutaneous sclerosing perineurioma in young patients without stigmata of neurofibromatosis. Histologically, these lesions were well‐circumscribed masses and were characterized by a variable number of epithelioid and spindle cells with wavy nuclei end elongated cytoplasmic processes embedded in a dense collagen stroma.Results:  These cells showed focal whorling formation, demonstrated robust immunoreactivity for EMA and CD99, and were uniformly negative for S‐100 protein, actin (HHF‐35), CD34, cytokeratin AE1‐3, and CD57.Conclusion:  We comment on the differential diagnosis of fibrous cutaneous lesions based on immunohistochemistry.
Widespread cutaneous and perioral metastases of mesothelioma
Authors: Cassarino David S. , Xue Wayne , Shannon Kevin J. 
Published: September 2003

Background:  Cutaneous involvement by mesothelioma represents a rare occurrence from an uncommon neoplasm. Most cases have resulted from local extension of an underlying body cavity mesothelioma or from surgical site contamination. We could only find six previously reported cases of distant cutaneous metastases of mesothelioma.Methods:  We describe a case of metastatic mesothelioma involving multiple skin sites and the lip in a 64‐year‐old man with an underlying primary pleural mesothelioma.Results:  A 64‐year‐old man presented with a lip lesion clinically diagnosed as keratoacanthoma vs. squamous cell carcinoma. Evaluation of the lip biopsy revealed tubulo‐glandular and acinar‐like arrangements of plump epithelioid cells with a hobnailed appearance, vesicular nuclei, and prominent nucleoli. The initial impression of metastatic carcinoma was revised to probable mesothelioma upon discovery of a previous history of pleural mesothelioma. Positive immunohistochemical stains for anti‐cytokeratin, anti‐calretinin, and HBME‐1 and negative stains for anti‐CEA, Leu‐M1, B72.3, and Ber‐Ep4 confirmed the diagnosis.Conclusion:  We report a rare example of multiple cutaneous metastases of mesothelioma. We also demonstrate the usefulness of relatively new and specific immunomarkers for mesothelioma vs. adenocarcinoma. Metastatic mesothelioma to the skin or lip is a very rare occurrence but should be considered in the differential diagnosis of malignant epithelioid neoplasms.
A novel epidermal nevus syndrome with congenital cylindromatous turban tumor
Authors: Regalado Jacinto J. 
Published: September 2003

Background:  Epidermal nevi (in the broad sense of epithelial nevi) may give rise to benign or malignant skin tumors. They may also be associated with anomalies of other organ systems in an epidermal nevus syndrome.Results:  This article describes a preterm infant with nevus sebaceus of the scalp and face, a large turban tumor with features of malignant cylindroma and multiple non‐cutaneous defects. These included skeletal, hematopoietic, hepatobiliary, and urinary anomalies. Severe secondary lesions were present (pulmonary hypoplasia due to oligohydramnios; cerebral infarcts probably related to the turban tumor). Karyotype was normal, and family history was negative.Conclusions:  This unique case is unlike any reported epidermal nevus syndrome. Similarly, there is no prior report of a congenital cylindroma, certainly not as a turban tumor, which implies very rapid growth. The presence of both overgrowth and undergrowth phenomena (e.g. hypoplastic urinary tract and biliary atresia) may reflect dysregulation of paracrine growth factors, presumably due to genetic mutation.
Intertriginous epidermal dysmaturation from pegylated liposomal doxorubicin
Authors: English Joseph C. , Toney Rachel , Patterson James W. 
Published: September 2003

Background:  A new formulation of doxorubicin (pegylated liposomal doxorubicin) has been developed to attenuate the systemic side effects produced by this agent. Although pegylated liposomal doxorubicin has a much lower risk for cardiotoxicity, it has been associated with cutaneous side effects that differ from, and may also be more frequent than, those produced by the free form of the drug.Methods:  We report a case of interface dermatitis with keratinocyte dysmaturation, limited to the intertriginous areas, in a patient who received pegylated liposomal doxorubicin, and we review the literature.Results:  It is possible that the enhanced delivery of doxorubicin in liposomal form promotes cutaneous side effects of the drug. We consider the possible mechanisms for keratinocyte dysmaturation produced by this form of doxorubicin.Conclusions:  Our findings further suggest that inflammatory changes seen on biopsy may not always allow a reliable histopathologic distinction between this chemotherapy effect and graft‐versus‐host disease.
Differential expression of α1 (IV) and α5 (IV) collagen chains in basal‐cell carcinoma
Authors: Quatresooz Pascale , Martalo Oriane , Piérard Gérald E. 
Published: September 2003

Background:  Basement membrane alterations are common in malignancies, and they may indicate tumoral aggressiveness. Distinct patterns of tumoral coverage by collagen IV were reported in nodular and aggressive basal‐cell carcinomas (BCCs). Differential expressions of α (IV) collagen chains were also shown on frozen sections. The aim of our work was to document the immunohistochemical expression of α1, α3, and α5 (IV) collagen chains in BCC after routine fixation and processing.Methods:  The patterns of distribution of α1 (IV), α3 (IV), and α5 (IV) collagen chains were studied in 20 formalin‐fixed and paraffin‐embedded BCCs showing different infiltrative patterns. One trichoblastoma was used as control.Results:  In nodular BCCs, the expression of α5 (IV) collagen chain was downregulated and uneven. By contrast, α1 (IV) collagen chain expression was preserved around these tumors similar to the surrounding skin. However, the α1 (IV) collagen chain expression was discontinuous or absent in BCC areas showing an infiltrative pattern of extension. The α3 chain was absent both underneath all BCCs and non‐neoplastic skin.Conclusions:  The basement membrane alterations around nodular BCCs involved more precisely the α5 (IV) collagen chains. Defects in α1 (IV) collagen chain expression seemed to be associated with a tumoral invasive and infiltrative pattern. The biological significance of these findings is unclear.
Characteristic immunohistochemical and ultrastructural findings indicate that Kindler's syndrome is an apoptotic skin disorder
Authors: Lanschuetzer C. M. , Muss W. H. , Emberger M. , Pohla‐Gubo G. , Klausegger A. , Bauer J. W. , Hintner H. 
Published: September 2003

Background:  Kindler's syndrome is a rare genodermatosis mainly characterized by the onset of skin blistering in early childhood, web formation of fingers and toes, photosensitivity, and progressive poikiloderma. There is still debate whether this disease represents a distinctive entity in the spectrum of congenital bullous poikilodermas or a variant of dystrophic epidermolysis bullosa.Objective:  To evaluate the recently proposed and debated characteristic immunohistochemical and ultrastructural features of Kindler's syndrome.Patient/methods:  Immunofluorescence (IF) antigen mapping and transmission electron microscopy (TEM) were performed on a skin specimen from non‐sun‐exposed inner aspect of the upper arm of a 49‐year‐old patient with characteristic clinical features of Kindler's syndrome.Results:  IF studies revealed focally an extensively broadened, partly reticular staining pattern in the dermoepidermal basement membrane zone (BMZ) with antibodies against laminin‐5 and type IV as well as type VII collagen. Anti‐α6 and β4 integrin staining revealed small gaps in the linear reactivity in the BMZ. Abundant keratin bodies, as detected by anti‐immunoglobulin M (IgM) staining, were focally present in the dermis, indicating prominent epidermal apoptosis. This was verified by a histochemical apoptosis stain [terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL) reaction]. Transmission electron microscopic examination showed manifold reduplications of the lamina densa (with attached anchoring fibrils) as well as a keratin body surrounded by a fibroblast in the upper dermis.Conclusion:  We present characteristic immunohistochemical and ultrastructural features of Kindler's syndrome identical to those described by Shimizu et al. (Arch Dermatol 1997; 133: 1111) and provide evidence that Kindler's syndrome might primarily be an apoptotic disorder of basal keratinocytes.
A single ring of charged amino acids at one end of the pore can control ion selectivity in the 5‐HT3 receptor
Authors: Thompson Andrew J , Lummis Sarah C R 
Published: September 2003

To determine the mechanisms by which cation‐ or anion‐specific channels select between these ions, we have examined the role of electrostatic factors in a typical ligand‐gated ion channel, the 5‐hydroxytryptamine3 (5‐HT3) receptor, by removal and/or insertion of rings of conserved charged residues at either end of the pore.
Neutralization of the negatively charged ring at the intracellular end of the channel (E−1′A) results in a nonselective channel (PNa/PCl=0.89).
Insertion of positively charged residues at the extracellular end of the pore either results in a nonfunctional receptor (A24′K) or one that remains cation‐selective (PNa/PCl=110; S19′R).
Combining the removal of a negatively charged ring (E−1′A) with the insertion of a positively charged ring (S19′R), however, results in a channel that is predominantly anion‐selective (PNa/PCl=0.37).
The data suggest that for the cation‐selective 5‐HT3 receptor, the control of selectivity exerted by charged rings at either end of the pore is dominated by the ring of negatively charged residues at the intracellular side of the channel. As changing the charge at this position has also been shown to change ionic selectivity in anion‐selective receptors, these data suggest that electrostatic factors can control selectivity in the whole Cys‐loop family.

British Journal of Pharmacology (2003) 140, 359–365. doi:10.1038/sj.bjp.0705424
A statin‐based inhibitor of lymphocyte function antigen‐1 protects against ischemia/reperfusion‐induced leukocyte adhesion in the colon
Authors: Wan Min Xiu , Schramm Rene , Klintman Daniel , Welzenbach Karl , Weitz‐Schmidt Gabriele , Thorlacius Henrik 
Published: September 2003

Statins are mainly used to control hypercholesterolemia; however, recent studies have also ascribed anti‐inflammatory effects to the statins. LFA703 is a novel statin‐derived compound, which potently inhibits lymphocyte function antigen‐1 (LFA‐1, CD11a/CD18) but does not affect HMG‐CoA reductase activity.
The objective of this study was to examine the anti‐inflammatory mechanisms of LFA703 in ischemia/reperfusion (I/R)‐induced leukocyte–endothelium interactions in the colon. For this purpose, the superior mesenteric artery was occluded for 30 min and leukocyte responses were analyzed in colonic venules after 120 min of reperfusion in mice using inverted intravital fluorescence microscopy.
First, the inhibitory mechanisms of LFA703 on leukocyte adhesion were investigated in vitro using a mouse CD4+8+ thymocyte cell line. Immunoneutralization of LFA‐1 and ICAM‐1 abolished leukocyte adhesion, whereas inhibition of VLA‐4 had no effect in this in vitro assay. Indeed, it was found that LFA703 dose‐dependently reduced LFA‐1‐dependent leukocyte adhesion to mouse endothelial cells in vitro with an IC50 of 3.2 μM.
I/R caused an increase in leukocyte rolling and adhesion in colonic venules. Immunoneutralization of LFA‐1 significantly reduced I/R‐induced leukocyte adhesion by 89% in colonic venules. In contrast, I/R‐provoked leukocyte rolling was insensitive to inhibition of LFA‐1 function.
Administration of 30 mg kg−1 of LFA703 decreased reperfusion‐induced leukocyte adhesion by more than 91%, while the level of leukocyte rolling was unchanged, suggesting that LFA703 effectively blocked LFA‐1‐dependent firm adhesion of leukocyte in the colon. However, LFA703 did not decrease the expression of LFA‐1 on circulating leukocytes.
This study demonstrates that LFA‐1 is indeed a critical adhesion molecule in mediating postischemic leukocyte adhesion in the colon. Moreover, this is the first study showing that a statin‐based synthetic compound has the capacity to abolish LFA‐1‐dependent leukocyte adhesion in I/R. These novel findings may have great implications in the clinical treatment of conditions associated with I/R‐induced tissue injury, such as organ transplantation, trauma and major surgery.

British Journal of Pharmacology (2003) 140, 395–401. doi:10.1038/sj.bjp.0705432
Involvement of EDHF in the hypotension and increased gastric mucosal blood flow caused by PAR‐2 activation in rats
Authors: Kawabata Atsufumi , Nakaya Yumiko , Kuroda Ryotaro , Wakisaka Mariko , Masuko Takashi , Nishikawa Hiroyuki , Kawai Kenzo 
Published: September 2003

Agonists for protease‐activated receptor‐2 (PAR‐2) cause hypotension and an increase in gastric mucosal blood flow (GMBF) in vivo. We thus studied the mechanisms underlying the circulatory modulation by PAR‐2 activation in vivo, especially with respect to involvement of endothelium‐derived hyperpolarizing factor (EDHF).
Arterial blood pressure and GMBF were measured in anesthetized rats in vivo. Vascular relaxation was assessed in the precontracted rat gastric arterial rings in vitro.
The PAR‐2‐activating peptide SLIGRL‐NH2 and/or trypsin, administered i.v., produced largely NO‐independent hypotension and increase in GMBF accompanied by decreased gastric mucosal vascular resistance (GMVR) in rats.
Combined administration of apamin and charybdotoxin, but not each of them, specifically abolished the hypotension, increased GMBF and decreased GMVR caused by the PAR‐2 agonists.
In the isolated rat gastric artery, SLIGRL‐NH2 elicited endothelium‐dependent relaxation even in the presence of an NO synthase inhibitor and indomethacin, which was abolished by apamin plus charybdotoxin.
Our data suggest involvement of apamin/charybdotoxin‐sensitive K+ channels in the PAR‐2‐triggered hypotension and increased GMBF, predicting a role of EDHF‐like factors.

British Journal of Pharmacology (2003) 140, 247–254. doi:10.1038/sj.bjp.0705433
Staurosporine induces rapid homotypic intercellular adhesion of U937 cells via multiple kinase activation
Authors: Cho Jae Youl , Katz David R , Chain Benjamin M 
Published: September 2003

Staurosporine is a broad‐specificity kinase inhibitor, which has acted as lead compound for the development of some novel cytotoxic compounds for treatment of cancer. This study investigates the unexpected observation that staurosporine can also induce homotypic cellular aggregation.
In this study, staurosporine is shown to activate rapid homotypic aggregation of U937 cells, at concentrations below those required to induce cell death. This activity is a particular feature of staurosporine, and is not shared by a number of other kinase inhibitors. The proaggregating activity of staurosporine is inhibited by deoxyglucose, cytochalasin B and colchicine. Staurosporine‐induced aggregation can be distinguished from that induced by the phorbol 12‐myristate 13‐acetate by faster kinetics and insensitivity to cycloheximide. Staurosporine induces translocation of conventional and novel, but not atypical isoforms of protein kinase C (PKC). Aggregation induced by staurosporine is inhibited by a number of inhibitors of PKC isoforms, and by inhibitors of protein tyrosine kinases. Staurosporine also induces rapid phosphorylation of ERK and p38, and inhibitors of both these enzymes block aggregation.
Staurosporine induces dysregulated activation of multiple kinase signaling pathways in U937 cells, and the combined activity of several of these pathways is essential for the induction of aggregation.

British Journal of Pharmacology (2003) 140, 269–276. doi:10.1038/sj.bjp.0705436
Agonist actions of dihydroergotamine at 5‐HT2B and 5‐HT2C receptors and their possible relevance to antimigraine efficacy
Authors: Schaerlinger B , Hickel P , Etienne N , Guesnier L , Maroteaux L 
Published: September 2003

The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occurrence of migraine attacks. Although still controversial, the prophylactic effect of this drug is believed to be caused through blockade and/or activation of numerous receptors including serotonin (5‐HT) receptors of the 5‐HT2 subtype.
To elucidate if 5‐HT2 receptors (5‐HT2Rs) may be involved in DHE prophylactic effect, we performed investigations aimed to determine the respective pharmacological profile of DHE and of its major metabolite 8′‐hydroxy‐DHE (8′‐OH‐DHE) at the 5‐HT2B and 5‐HT2CRs by binding, inositol triphosphate (IP3) or cyclic GMP (cGMP) coupling studies in transfected fibroblasts.
DHE and 8′‐OH‐DHE are competitive compounds at 5‐HT2B and 5‐HT2CRs. 8′‐OH‐DHE interaction at (5‐HT2BRs) was best fitted by a biphasic competition curve and displayed the highest affinity with a Ki of 5 nM. These two compounds acted as agonists for both receptors in respect to cGMP production with pEC50 of 8.32±0.09 for 8′‐OH‐DHE at 5‐HT2B and 7.83±0.06 at 5‐HT2CRs.
Knowing that the antimigraine prophylactic effect of DHE is only observed after long‐term treatment, we chronically exposed the recombinant cells to DHE and 8′‐OH‐DHE. The number of 5‐HT2BR‐binding sites was always more affected than 5‐HT2CRs. At 5‐HT2BRs, 8′‐OH‐DHE was more effective than DHE, with an uncoupling that persisted for more than 40 h for IP3 or cGMP. By contrast, the 5‐HT2CR coupling was reversible after either treatment.
Chronic exposure to 8′‐OH‐DHE caused a persistent agonist‐mediated desensitisation of 5‐HT2B, but not 5‐HT2CRs. This may be of relevance to therapeutic actions of the compound.

British Journal of Pharmacology (2003) 140, 277–284. doi:10.1038/sj.bjp.0705437
Spinal administration of lipoxygenase inhibitors suppresses behavioural and neurochemical manifestations of naloxone‐precipitated opioid withdrawal
Authors: Trang Tuan , Sutak Maaja , Quirion Remi , Jhamandas Khem 
Published: September 2003

This study investigated the role of spinal lipoxygenase (LOX) products in the induction and expression of opioid physical dependence using behavioural assessment of withdrawal and immunostaining for CGRP and Fos protein expression in the spinal cord.
Administration of escalating doses (5–50 mg kg−1; i.p.) of morphine for 5 days markedly elevated CGRP‐like immunoreactivity in the dorsal horn of the rat spinal cord. Naloxone (2 mg kg−1; i.p.) challenge precipitated a robust withdrawal syndrome that depleted CGRP‐like immunoreactivity and increased the number of Fos‐like immunoreactive neurons in the dorsal horn.
Intrathecal administration of NDGA (10, 20 μg), a nonselective LOX inhibitor, AA‐861 (1.5, 3 μg), a 5‐LOX selective inhibitor, or baicalein (1.4, 2.8 μg), a 12‐LOX selective inhibitor, concurrently with systemic morphine for 5 days or as a single injection immediately preceding naloxone challenge, blocked the depletion of CGRP‐like immunoreactivity, prevented increase in the number of Fos‐like immunoreactive neurons in the dorsal horn, and significantly attenuated the morphine withdrawal syndrome.
The results of this study suggest that activity of LOX products, at the spinal level, contributes to the expression of opioid physical dependence, and that this activity may be expressed through increased sensory neuropeptide release.

British Journal of Pharmacology (2003) 140, 295–304. doi:10.1038/sj.bjp.0705440
Effects of etherlipid analogs on cell membrane functions
Authors: Berkovic Dinko , Wernicke Jan Heino , Fleer Eduard A. M. 
Published: September 2003

Hexadecylphosphocholine and other etherlipid‐derived substances show a pronounced antiproliferative activity on neoplastic cells and a broad spectrum of other biological effects on many cell types in vitro and in vivo. Though the precise molecular mechanism by which these etherlipid analogs act still remains unresolved, it seems clear that it most probably involves some essential function of the cell membrane.We investigated the effect of different etherlipids with and without cytotoxic activity in etherlipid‐susceptible and ‐resistant tumor cell lines on three important membrane functions. We observed various inhibitory activities on endocytosis and the uptake of small precursor molecules as sugars, amino acids, and alcohols by toxic and nontoxic substances in resistant as well as susceptible cells. There was no correlation between the antiproliferative characteristics of the compounds and the effects on these membrane transport functions. Furthermore, the substances reduced the number of membrane tumor necrosis factor‐α receptors regardless of their antiproliferative properties. The results of these investigations suggest that etherlipid analogs may interfere with many membrane functions in an unspecific manner. Therefore, many of the previously reported biological effects of etherlipids have to be viewed under a different light. Future investigation on these compounds should always contain appropriate control substances and cell models to really prove the specificity of the observed effects.
Protein–protein interactions involving inducible nitric oxide synthase
Authors: Zhang W. , Kuncewicz T. , Yu Z.‐Y. , Zou L. , Xu X. , Kone B. C. 
Published: September 2003

AbstractAim:  Nitric oxide (NO) is a signaling and effector molecule that contributes to multiple physiological and pathophysiological processes in the kidney, vasculature, and other tissues. High output NO generation by inducible NO synthase (iNOS) participates in host defense against pathogens and contributes to tissue injury during inflammatory states. Because of its potent reactivity and diffusibility, NO generation by iNOS is subject to multiple levels of regulation, inculding transcriptional, translational, and post‐translational controls, inculding protein‐protein interactions. This review examines the experimental basis for these protein‐protein interactions and their known and potential importance for kidney and vascular physiology.Methods:  Analysis of the biomedical literature in the area.Results:  iNOS interacts with the inhibitory molecules Kalirin and NOS‐associated protien 1.10 kd (NAP110), which inhibit iNOS homodimerization, as well as activator proteins, the Rac‐GTPases. Interactions with caveolin‐1 control the intracellular locale and degradation of iNOS in tumor cells. In polarized epithelial cells, associations of iNOS with the scaffolding protien EBP50 position iNOS in the apical membrane near key ion transport proteins that also interact with EPB50. In addition, protein‐protein interactions of proteins governing iNOS transcription function to specify activation or suppression of iNOS induction by cytokines.Conclusion:  Interactions of iNOS with a diverse group of heterologous proteins provides a selective mechanism to control the activity, spatial distribution, and proximity of iNOS to intended targets, while potentially limiting autotoxicity to the iNOS‐expressing cell.