bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor-Derived Tissue FactorBearing Microparticles Are Associated With Venous Thromboembolic Events in Malignancy
Authors: Zwicker Jeffrey I. , Liebman Howard A. , Neuberg Donna , Lacroix Romaric , Bauer Kenneth A. , Furie Barbara C. , Furie Bruce
Published: October 2009

Purpose: Despite the strong association between malignant disease and thromboembolic disorders, the molecular and cellular basis of this relationship remains uncertain. We evaluated the hypothesis that tumor-derived tissue factorbearing microparticles in plasma contribute to cancer-associated thrombosis.

Experimental Design: We developed impedance-based flow cytometry to detect, quantitate, and size microparticles in platelet-poor plasma. We evaluated the number of tissue factorbearing microparticles in a cohort of cancer patients of different histologies (N = 96) and conducted a case-control study of 30 cancer patients diagnosed with an acute venous thromboembolic event (VTE) compared with 60 cancer patients of similar age, stage, sex, and diagnosis without known VTE, as well as 22 patients with an idiopathic VTE.

Results: Tissue factorbearing microparticles were detected in patients with advanced malignancy, including two thirds of patients with pancreatic carcinoma. Elevated levels of tissue factorbearing microparticles were associated VTE in cancer patients (adjusted odds ratio, 3.72; 95 confidence interval, 1.18-11.76; P = 0.01). In cancer patients without VTE, a retrospective analysis revealed a 1-year cumulative incidence of VTE of 34.8 in patients with tissue factorbearing microparticles versus 0 in those without detectable tissue factorbearing microparticles (Gray test P = 0.002).The median number of tissue factorbearing microparticles in the cancer VTE cohort (7.1 104 microparticles/L) was significantly greater than both the idiopathic VTE and cancerno VTE groups (P = 0.002 and P = 0.03, respectively). Pancreatectomy in three patients eliminated or nearly eliminated these microparticles which coexpressed the epithelial tumor antigen, MUC-1.

Conclusion: We conclude that tumor-derived tissue factorbearing microparticles are associated with VTE in cancer patients and may be central to the pathogenesis of cancer-associated thrombosis. (Clin Cancer Res 2009;15(22):683040)
NKG2D Ligand Expression in Human Colorectal Cancer Reveals Associations with Prognosis and Evidence for Immunoediting
Authors: McGilvray Roger W. , Eagle Robert A. , Watson Nicholas F.S. , Al-Attar Ahmad , Ball Graham , Jafferji Insiya , Trowsdale John , Durrant Lindy G.
Published: October 2009

Purpose: NKG2D (natural killer group 2, member D) binds to cellular ligands of the MIC and ULBP/RAET family. These ligands have restricted expression in normal tissue, but are frequently expressed on primary tumors. The role of NKG2D ligands is thought to be important in carcinogenesis but its prognostic effect has not been investigated in such a large cohort.

Experimental Design: In our study, 462 primary colorectal tumors were screened for the expression of all MIC/ULBP/RAET proteins and NK cell infiltration. Tumor microarray technology was used for the purpose of this investigation.

Results: NKG2D ligands were expressed by the majority of colorectal tumors; however, the level of expression varied considerably. High expression of MIC (68 versus 56 months) or RAET1G (74 versus 62 months) showed improved patient survival. Tumors expressing high levels of MIC and RAET1G showed improved survival of 77 months over tumors that expressed high levels of one ligand or low levels of both. High-level expression of all ligands was frequent in tumor-node-metastasis stage I tumors, but became progressively less frequent in stages II, III, and IV tumors. Expression of MIC was correlated with NK cellular infiltration.

Conclusion: The observations presented are consistent with an immunoediting mechanism that selects tumor cells that have lost or reduced their expression of NKG2D ligands. The combination of MIC and tumor-node-metastasis stage was found to be the strongest predictor of survival, splitting patients into eight groups and suggesting prognostic value in clinical assessment. Of particular interest were stage I patients with low expression of MIC who had a similar survival to stage III patients, and may be candidates for adjuvant therapy. (Clin Cancer Res 2009;15(22):69937002)
Altered Tissue 3′-Deoxy-3′-[18F]Fluorothymidine Pharmacokinetics in Human Breast Cancer following Capecitabine Treatment Detected by Positron Emission Tomography
Authors: Kenny Laura M. , Contractor Kaiyumars B. , Stebbing Justin , Al-Nahhas Adil , Palmieri Carlo , Shousha Sami , Coombes R. Charles , Aboagye Eric O.
Published: October 2009

Purpose: We showed in preclinical models that thymidylate synthase (TS) inhibition leads to redistribution of the nucleoside transporter, ENT1, to the cell membrane and hence increases tissue uptake of [18F]fluorothymidine (FLT). In this study, we assessed for the first time the altered pharmacokinetics of FLT in patients following administration of capecitabine, a drug whose mode of action has been reported to include TS inhibition.

Experimental Design: We analyzed 10 lesions from six patients with breast cancer by positron emission tomography before and after treatment with capecitabine. Although drug treatment did not alter tumor delivery pharmacokinetic variables (K1 and permeability product surface area) or blood flow, tumor FLT retention variables increased with drug treatment in all but one patient.

Results: The baseline average standardized uptake value at 60 minutes, rate constant for the net irreversible transfer of radiotracer from plasma to tumor (Ki), and unit impulse response function at 60 minutes were 11.11 × 10−5 m2/mL, 4.38 × 10−2 mL plasma/min/mL tissue, and 4.93 × 10−2/min, respectively. One hour after capecitabine administration, the standardized uptake value was 13.55 × 10−5 m2/mL (P = 0.004), Ki 7.40 × 10−2 mL plasma/min/mL tissue (P = 0.004), and impulse response function was 7.40 × 10−2/min (P = 0.002). FLT pharmacokinetics did not change in normal tissues, suggesting that the effect was largely restricted to tumors (P = 0.55).

Conclusions: We have identified FLT positron emission tomography retention parameters that could be used in future early clinical studies to measure the pharmacodynamics of TS inhibitors, as well as for identifying patients who are unlikely to benefit from TS inhibition. (Clin Cancer Res 2009;15(21):6649–57)
Rituximab-Mediated Cell Signaling and Chemo/Immuno-sensitization of Drug-Resistant B-NHL Is Independent of Its Fc Functions
Authors: Vega Mario I. , Huerta-Yepez Sara , Martinez-Paniagua Melisa , Martinez-Miguel Bernardo , Hernandez-Pando Rogelio , González-Bonilla Cesar R. , Chinn Paul , Hanna Nabil , Hariharan Kandasamy , Jazirehi Ali R. , Bonavida Benjamin
Published: October 2009

Purpose: Rituximab [chimeric anti-CD20 monoclonal antibody], alone or combined with chemotherapy, is used in the treatment of non–Hodgkin's lymphoma (NHL). Rituximab binds to CD20 and inhibits intracellular survival/growth pathways leading to chemo/immunosensitization of tumor cells in vitro. The contribution of rituximab Fc-FcR interaction in signaling is not known. This study examined the role of Fc-FcR interactions in rituximab-induced signaling using rituximab (Fab')2 fragments as well as rituximab devoid of the CH2 Fc-binding domain (CH2−).

Experimental Design: Rituximab (CH2−) and rituximab (Fab')2 were tested for their activity on B-NHL cell lines. Cell signaling and sensitization to chemotherapy and immunotherapy were examined. The in vitro studies were validated in mice bearing tumor xenografts.

Results: Although the modified antibodies were defective in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity functions, they retained all other biological activities such as inhibition of cell proliferation, induction of cell aggregation, and apoptosis induction. In addition, similar to rituximab, the modified antibodies inhibited the activity of cell survival/growth pathways and their associated transcription factors (e.g., NF-κB, YY1, SP-1), and signal transducers and activators of transcription 3 (STAT-3), and downregulated the expression of antiapoptotic gene products, such as Bcl-2/Bclxl, which regulate drug resistance. The modified antibodies, similar to rituximab, sensitized resistant B-NHL cells to both CDDP and Fas ligand–induced apoptosis. Furthermore, treatment of nude mice bearing Raji tumor cell xenografts with the combination of rituximab (Fab')2 or rituximab and CDDP resulted in similar and significant inhibition of tumor growth.

Conclusion: These findings reveal that rituximab-mediated inhibition of intracellular signaling pathways and leading to chemo/immuno-sensitization of resistant B-NHL is Fc independent. (Clin Cancer Res 2009;15(21):6582–94)
Serum Molecular Signatures of Weight Change during Early Breast Cancer Chemotherapy
Authors: Keun Hector C. , Sidhu Jasmin , Pchejetski Dmitry , Lewis Jacqueline S. , Marconell Helena , Patterson Michael , Bloom Steven R. , Amber Vian , Coombes R. Charles , Stebbing Justin
Published: October 2009

Purpose: Weight gain in women receiving chemotherapy for breast cancer is associated with a higher risk of recurrence but its mechanisms are poorly understood.

Experimental Design: To investigate this, we assessed the metabolic, cytokine, and appetite-related peptide alterations during adjuvant chemotherapy for early breast cancer in postmenopausal women, and correlated these with body mass measurements. Specifically, we performed global metabolic profiling using 1H-nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin immunoreactivity, RIAs for GLP-1 and peptide YY, and electrochemiluminescent cytokine analyses (tumor necrosis factor-α and interleukin-6) on sequential samples.

Results: In those who gained >1.5 kg, several metabolite levels were positively associated with weight gain, specifically lactate, which was 63.5% greater in patients with increased body weight during chemotherapy compared with those with no weight gain (P < 0.01; the prespecified primary end point). A strong correlation (r = 0.7, P < 0.001) was detected between the rate of weight change and serum lactate levels, and on average, lactate levels exhibited the greatest metabolic response to chemotherapy, increasing by up to 75%. Normalized levels of peptide YY were also observed to be elevated in patients not gaining weight posttreatment (+30% compared with −7% for the weight gain group; P < 10−4). Baseline lactate, alanine, and body fat were all prognostic for weight gain (area under the receiver operator characteristic curves, >0.77; P < 0.05). No associations were observed between any other parameter and weight gain, including cytokine levels.

Conclusions: Metabonomics identifies excess energy expenditure pathways perturbed during chemotherapy for breast cancer, and establishes a significant association between serum lactate, body fat, and substantive weight gain during chemotherapy. (Clin Cancer Res 2009;15(21):6716–23)
Enhancing Cancer Vaccine Efficacy via Modulation of the Tumor Microenvironment
Authors: Disis Mary L.
Published: October 2009

The development of therapeutic cancer vaccines is impacted by immunosuppressive elements in the tumor microenvironment. Most immunogenic cancer proteins are “self,” therefore, peripheral tolerance contributes substantially to tumor immune escape. Transforming growth factor β (TGFβ) actively modulates both inflammation and tolerance induction. Combining vaccination with agents that disarm TGFβ will enhance vaccine efficacy. (Clin Cancer Res 2009;15(21):1–3) (Clin Cancer Res 2009;15(21):6476–8)
Has Quantitative Multimodal Imaging of Treatment Response Arrived?
Authors: Yankeelov Thomas E. , Gore John C.
Published: October 2009

Although there have been dramatic increases in the range and quality of information available from noninvasive imaging methods, their application in clinical trials has been limited. One promising approach is to apply imaging techniques in preclinical studies designed to mimic a corresponding clinical trial in order to inform that trial. (Clin Cancer Res 2009;15(21):6473–5)
Estrogenic Promotion of ErbB2 Tyrosine Kinase Activity in Mammary Tumor Cells Requires Activation of ErbB3 Signaling
Authors: Liu Bolin , Ordonez-Ercan Dalia , Fan Zeying , Huang Xiaoping , Edgerton Susan M. , Yang XiaoHe , Thor Ann D.
Published: October 2009

Increasing evidence suggests molecular interactions between erbB2 and other receptor tyrosine kinases, and estrogenic compounds and their cognate receptors. We have recently reported that downregulation of erbB3 abrogates erbB2-mediated tamoxifen resistance in breast cancer cells. On the basis of these data, we hypothesized that erbB3 may play a major role connecting these two sentinel pathways. Interactions were studied using mammary/breast cancer cell lines from wild-type rat c-neu gene transgenic mice and humans. Estradiol promoted cell proliferation and activated erbB2/neu tyrosine kinase, Akt, and mitogen-activated protein kinase signaling exclusively in mammary and breast epithelial cell lines with coexpression of both erbB2 and erbB3. Estradiol action was independent of the transgene promoter (MMTV-LTR) activity, both in vitro and in vivo, as well as c-neu transgene or endogenous erbB2 gene expression. Estrogen induction of cell growth promotion, erbB2/neu activation, and downstream signaling was abrogated by blockade of estrogen receptor (ER) with the pure ER antagonist ICI 182,780 or knockdown of erbB3 expression via specific siRNA. These data suggest that activation of both ER and erbB2/erbB3 signaling is requisite for estrogen-induced mitogenesis and erbB2/neu tyrosine kinase activation.(Mol Cancer Res 2009;7(11):1882–92)
z-Leucinyl-Leucinyl-Norleucinal Induces Apoptosis of Human Glioblastoma Tumor–Initiating Cells by Proteasome Inhibition and Mitotic Arrest Response
Authors: Monticone Massimiliano , Biollo Emanuela , Fabiano Andrea , Fabbi Marina , Daga Antonio , Romeo Francesco , Maffei Massimo , Melotti Alice , Giaretti Walter , Corte Giorgio , Castagnola Patrizio
Published: October 2009

γ-secretase inhibitors have been proposed as drugs able to kill cancer cells by targeting the NOTCH pathway. Here, we investigated two of such inhibitors, the Benzyloxicarbonyl-Leu-Leu-Nle-CHO (LLNle) and the N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), to assess whether they were effective in killing human glioblastoma tumor–initiating cells (GBM TIC) in vitro. We found that only LLNle was able at the micromolar range to induce the death of GBM TICs by apoptosis. To determine the cellular processes that were activated in GBM TICs by treatment with LLNle, we analyzed the amount of the NOTCH intracellular domain and the gene expression profiles following treatment with LLNle, DAPT, and DMSO (vehicle). We found that LLNIe, beside inhibiting the generation of the NOTCH intracellular domain, also induces proteasome inhibition, proteolytic stress, and mitotic arrest in these cells by repressing genes required for DNA synthesis and mitotic progression and by activating genes acting as mitotic inhibitors. DNA content flow cytometry clearly showed that cells treated with LLNle undergo arrest in the G2-M phases of the cell cycle. We also found that DAPT and L-685,458, another selective Notch inhibitor, were unable to kill GBM TICs, whereas lactacystin, a pure proteasome inhibitor, was effective although at a much less extent than LLNle. These data show that LLNle kills GBM TIC cells by inhibiting the proteasome activity. We suggest that LLNle, being able to target two relevant pathways for GBM TIC survival, may have a potential therapeutic value that deserves further investigation in animal models. (Mol Cancer Res 2009;7(11):1822–34)
Deguelin Inhibits Growth of Breast Cancer Cells by Modulating the Expression of Key Members of the Wnt Signaling Pathway
Authors: Murillo Genoveva , Peng Xinjian , Torres Karen E.O. , Mehta Rajendra G.
Published: October 2009

An emphasis in early detection and more effective treatments has decreased the mortality rate of breast cancer. Despite this decrease, breast cancer continues to be the leading cause of death among women between 40 and 55 years of age and is the second overall cause of death among women. Hence, the aim of the present study was to assess the therapeutic efficacy of deguelin, a rotenoid isolated from several plant species, which has been reported to have chemopreventive and/or chemotherapeutic effects in skin, mammary, colon, and lung cancers. The effect of deguelin on cell proliferation was evaluated using four human breast carcinoma cell lines (MCF-7, BT474, T47D, and MDA-MB-231) by cell count and MTT. Moreover, apoptosis was evaluated by acridine/ethidium staining and DNA laddering. Gene expression changes following deguelin treatment in MDA-MB-231 cells was assessed through microarray analysis. Deguelin at 1 μmol/L was found to inhibit the growth of the breast cancer cell lines tested with a range of 37% to 87%. The highest inhibition was noted for the MDA-MB-231 cell line (MDA-MB-231>BT474>MCF7>T47D>MCF12F). An arrest at the S phase of the cell cycle and apoptosis were shown in the MDA-MB-231 cells treated with deguelin. The microarray profile indicated differential expression of two independent pathways, including clusters of apoptosis and Wnt/β-catenin signaling genes in cells as a result of deguelin treatment. These studies support the antiproliferative effects of deguelin in human breast cancer cells and, perhaps more importantly, illustrate novel actions by deguelin in the Wnt signaling pathway.
The 450-Band Resolution G- and R-Banded Standard Karyotype of the Donkey (Equus asinus, 2n = 62)
Authors: Di Meo G.P. , Perucatti A. , Peretti V. , Incarnato D. , Ciotola F. , Liotta L. , Raudsepp T. , Di Berardino D. , Chowdhary B. , Iannuzzi L.
Published: October 2009

Donkey chromosomes were earlier characterized separately by C-, G- and R-banding techniques. However, direct comparisons between G- and R-banding patterns have still not been carried out in this species. The present study reports this comparison at the 450-band level by using replication G- and R-banding patterns. Two sets of synchronized lymphocyte cultures were set up to obtain early (GBA+CBA-banding) and late (RBA-banding) BrdU incorporation. Slides were stained with acridine orange and observed under a fluorescence microscope. Reverse GBA+CBA- and RBA-banded karyotypes at the 450-band level were constructed. To verify G- and R-banding patterns in some acrocentric chromosomes, sequential GBA+CBA/Ag-NORs and RBA/Ag-NORs were also performed. The results of CBA-banding patterns obtained in 12 animals from 2 breeds showed a pronounced polymorphism of heterochromatin, especially in EAS1q-prox. Ideogrammatic representations of G- and R-banded karyotypes were constructed using only one common G- and R-banding nomenclature. In the present study both G- and R-banding patterns and relative ideograms are presented as standard karyotype for this species at the 450-band level.
Genetic Mapping of the Ornithine Decarboxylase (odc) Gene Complex in Rainbow Trout (Oncorhynchus mykiss)
Authors: Tuziak S.M. , Moghadam H.K. , Danzmann R.G.
Published: October 2009

Ornithine decarboxylase (odc) and its associated gene complex, including antizymes of ODC and inhibitors of the antizymes, play a key role in regulating the overall polyamine levels (i.e., putrescine) in cells. Polyamine production levels are intricately coupled to mitotic and cellular turnover rates. Hence, these genes may be important candidates of growth regulation in vertebrates, if their chromosomal locations coincide with known quantitative trait locus (QTL) regions influencing growth traits. Here we report the genetic mapping of multiple duplicated forms of genes within this complex to previously known life-history and growth QTL regions in rainbow trout (Oncorhynchus mykiss). Specifically, duplicated copies of the 2 antizyme genes map to Om-8/9/24, while antizyme inhibitor and odc duplicates map to Om-27/31 and Om-14/25, respectively. All sets of paralogous mapping locations correspond to ancestrally duplicated synteny regions within the genome of rainbow trout (i.e., ancestral A, B, GH/I and M linkage groups).
Oxidative Stress Markers and C-Reactive Protein in Pediatric Patients on Hemodialysis
Authors: Elshamaa Manal F. , Sabry Samar , Nabih Mohamed , Elghoroury Eman A. , El-Saaid Gamila S. , Ismail Amany A.G.
Published: October 2009

Background: Pediatric patients with end-stage renal disease undergoing hemodialysis (HD) are exposed to oxidative stress associated with an impairment of antioxidant defense and an overproduction of oxidative stress markers. Oxidative stress plays a significant role in the development of inflammation in these patients. Objectives: The high incidence of cardiovascular disease in HD pediatric patients is now well established and the involvement of oxidative stress has been hypothesized. This study focuses on a comparison of plasma total antioxidant capacity (TAC) and lipid peroxidation product and evaluates the relationship between these parameters and high-sensitivity C-reactive protein (hsCRP) in pediatric patients on HD. Subjects and Methods: Plasma TAC, lipid peroxidation products, malondialdehyde (MDA) as well as hsCRP were determined in 30 pediatric patients on HD and in 20 healthy controls (HC). Results: TAC and MDA levels were significantly higher in children on HD than in the HC (p < 0.001). The hsCRP values were also significantly higher in HD patients than in HC (p < 0.001). The percentage of HD pediatric patients with CRP >10 mg/l was 30%. The concentrations of TAC and MDA correlated positively with hsCRP in HD patients (TAC: r = 0.52, p < 0.08; MDA: r = 0.75, p < 0.04), but not in HC. Conclusion: Our study demonstrates an increase in oxidative stress in children on HD and that the susceptibility to oxidative stress is strongly related to the levels of MDA produced in plasma. hsCRP levels are higher in children on HD than in HC and this is indicative of a higher degree of inflammatory activity in the former patients. These profound disturbances in oxidative stress markers may provide an explanation for the cardiovascular complications in HD patients.
Endothelial Keratoplasty without Descemet’s Membrane Stripping: Histologic and Ultrastructural Findings
Authors: Nikolic Ljubisa , Jovanovic Vesna , Lackovic Vesna , Todorovic Vera
Published: October 2009

Aim: To report histologic and ultrastructural findings of endothelial keratoplasty (EK) performed without Descemet’s membrane stripping. Methods: Clinical techniques, histology, and transmission electron microscopy. Results: A 55-year-old woman was referred to us, after 2 unsuccessful penetrating keratoplasties (PKs), for pseudophakic bullous keratopathy. An 8.0-mm EK without Descemet’s membrane stripping was performed, and clarity was restored to the failed penetrating regraft. A year later, the lamellar graft failed, and a third PK was performed for intractable corneal edema. Light microscopy of a semi-thin section of the trephined corneal button showed both the recipient’s and the donor’s Descemet’s membrane, the well-preserved structure of the full-thickness graft, and marked edema of the adherent stromal carrier of the endothelial transplant. The host endothelium was absent at the interface, and the donor endothelium was atrophic. Electron microscopy revealed regularity and even spacing of collagen fibrils as well as quiet keratocytes on both sides of Descemet’s membrane at PK-EK interface. Conclusion: These findings suggest a lack of proliferation and hypercellular scarring, and offer further support to the already proven merits of EK.
Becker’s Nevus and Malignant Melanoma
Authors: Fehr B. , Panizzon R.G. , Schnyder U.W.
Published: October 2009

We describe 9 patients who presented Becker’s nevus (BN) together with a malignant melanoma (MM). Eight patients were male. In 5 patients the MM was on the same body site as the BN. The melanoma was of the superficial-spreading type in 7 cases and in 1 patient was within the BN. Twice a dysplastic-nevus syndrome was diagnosed and in 2 patients a familial melanoma. To the best of our knowledge this is the first report of the co-occurrence of BN and MM.
Aneurysm Associated with Chronic Mucocutaneous Candidiasis during Long-Term Therapy with Ketoconazole
Authors: Leroy D. , Dompmartin A. , Houtteville J.P. , Theron J.
Published: October 2009

A little girl who was suffering from chronic mucocutaneous candidiasis also had a cellular immune deficiency and undetectable IgA levels. She was treated continuously for 6 years with ketoconazole at the same dosage of 200 mg/day. She was rapidly clear from infection and dit not relapse although her immune abnormalities persisted. During this long-term therapy, voluminous fusiform intracranial aneurysm appeared, causing a paresis of the four limbs. Are they mycotic aneurysms?
Epidermal Proliferation and Accumulation of Polymorphonuclear Leukocytes in the Psoriatic Lesion
Authors: Beurskens T. , Chang A. , van Erp P.E.J. , van de Kerkhof P.C.M.
Published: October 2009

Biopsies were removed from the margin of plaques in 11 untreated psoriatic patients, and 8-μm sections prepared using the cryostat. Alternate sections were stained with H and E to assess the accumulation of polymorphonuclear leukocytes.The remaining sections were stained with the monoclonal antibody Ki67 in order to determine the number of cycling epidermal cells. In areas where polymorphonuclear leukocytes occurred in the stratum Malpighi the number of cycling epidermal cells was relatively low. In contrast, a positive correlation was shown between the density of microabscesses of Munro and the number of cycling epidermal cells. The clinically uninvolved skin of psoriatic patients shows a moderate enhancement of epidermal growth in the absence of any infiltrate. In the lesional skin the recruitment of cycling epidermal cells does not coincide with the invasion of polymorphonuclear leukocytes into the epidermis, but rather follows the penetration of these cells.
Acné ‘en Plaque’ and Acquired Ichthyosis
Authors: Salomon Denis , Harms Monika , Saurat Jean-Hilaire
Published: October 2009

A 50-year-old man with no past history of acne vulgaris developed at the age of 47 years acneiform lesions focally distributed on the trunk, acquired ichthyosis and lichenoid lesions without history of toxic exposure. This may represent either an unnoticed exposure to a toxic substance or a paraneoplastic syndrome.
Dysplastic Nevi and Germ Cell Tumors of the Testis – a Possible Further Tumor in the Spectrum of Associated Malignancies in Dysplastic Nevus Syndrome
Authors: Sigg Christian , Pelloni Francesco
Published: October 2009

Even though the exact spectrum of tumors is not yet defined in the dysplastic nevus syndrome (DNS), the increasing frequency of associated cancers is remarkable. The observation of 4 patients with sporadic form of DNS suffering from seminoma or embryonal carcinoma of the testicle suggests that germ cell tumors of the testis represent another form of associated cancer in DNS.
Fibronectin in Pemphigus
Authors: Hunziker Thomas , Morgenthaler Jean-Jacques , Gerber Heinz A.
Published: October 2009

In the skin organ culture model of pemphigus, fibronectin concentrations of 300 and 500 μg/ml inhibited pemphigus plasma-induced acantholysis and intraepidermal binding of the pemphigus antibodies examined by direct immunofluorescence. A direct interaction of fibronectin with pemphigus antibodies could not be demonstrated by chromatography of pemphigus plasma on immobilized fibronectin or by incubation with fibronectin and subsequent precipitation with antifibronectin. We then measured fibronectin concentrations in the plasma of 15 patients suffering from various types of pemphigus and presenting different activities of their disease. Immunoreactive fibronectin levels in untreated patients with active disease were generally in the low normal or even clearly in the subnormal range. They had the tendency to decrease when the disease subsided during therapy with high doses of glucocorticoids, sometimes in combination with azathioprine. The fibronectin concentration in the blister fluid of a patient with acute, untreated pemphigus vulgaris was similar to that in a plasma sample taken at the same time. Skin biopsies of pemphigus patients exhibited an essentially normal fibronectin pattern in direct immunofluorescence. We discuss a possible protective role of fibronectin in pemphigus e.g., by reducing the permeability for pemphigus antibodies in the dermal-epidermal junction zone.
Vasculite cutanée révélatrice d’une hépatite chronique: à propos de 2 cas
Authors: de Maubeuge J. , Reding P. , Tielemans C. , Dratwa M. , Van Laethem Y. , Achten G.
Published: October 2009

2 cases of cutaneous vasculitis associated with chronic hepatitis and mixed cryoglobulinaemia are reported. Further studies revealed in the first case hypocomplementaemia and glomerulonephritis. The cutaneous lesions of this patient responded dramatically to plasma exchange whereas prednisolone 20 mg/day and azathioprine 50 mg/day for 10 months showed no effect. The second case (chronic active hepatitis with acute colitis) responded well to prednisolone and azathioprine. The cutaneous lesions (vascularitis) may be the only clinical symptom of a chronic hepatitis and the study of those cases sometimes allows an early diagnosis of renal failure to be made.
Nævus anémique généralisé acquis
Authors: Dupré A. , Bonafe J.L. , Jouas H.
Published: October 2009

We are reporting a case of generalized nevus anemicus in an adult, which was not associated with phacomatosis or pheochromocytoma. The pharmacological investigation of the vasomotricity showed permanent vasoconstriction in the anemic areas. The cutaneous levels of catecholamines were seven times as high in the anemic areas as in the sound areas. We have investigated a possible increase in the number of APUD by a histochemical method (Grimelius’s stain). This possible increase might have accounted for a local hypersecretion of catecholamines. Our investigation was negative. No etiological mechanism can be suggested.
Focal Epithelial Hyperplasia
Authors: Laskaris George C. , Papanicolaou Stavros J. , Angelopoulos Angelos P.
Published: October 2009

A typical case of focal epithelial hyperplasia in a 56-year-old white female is reported. It is the first case described among the Greek population. Approximately 60 discrete and clustered papules were seen on the patient’s lower lip, commissures and buccal mucosa. No evidence of the disease was found in any member of the patient’s family. 4 months after the diagnosis, the lesions showed considerable regression.
Multiple Endocrine Neoplasia, Type IIb
Authors: Ayala F. , De Rosa G. , Scippa L. , Vecchio P.
Published: October 2009

Multiple endocrine neoplasia, type IIb, is a rare syndrome characterized by mucosal neuromas, medullary thyroid carcinoma (MTC), pheochromocytoma and somatic abnormalities. A case of a 10-year-old girl with multiple mucosal neuromas and bilateral MTC is reported. The presumptive diagnosis of MTC was made on the basis of abnormal basal values of calcitonin and increased calcitonin secretion after pentagastrin injection. The manifestations of the syndrome are summarized, and the importance of repeated evaluation of thyroidal C-cell and adrenal medullary function in patients with the characteristic aspect of the syndrome is emphasized.
Ainhum, Trichosporosis and Z-Plasty
Authors: Kamalam A. , Thambiah A.S.
Published: October 2009

Association of ainhum and cutaneous trichosporosis by Trichosporon cutaneum in 4 cases are reported. Z-plasty in 1 along with local application of dequalenium chloride were helpful in relieving the disorder. The possible role played by Trichosporon cutaneum in initiating or aggravating ainhum is emphasized.
Familial Koilonychia
Authors: Almagor G. , Haim S.
Published: October 2009

Familial koilonychia involving 7 members in 3 generations is reported, one of them was complicated with an episode of bacterial infection of all fingernails. The familial distribution of the process in this report suggests an autosomal dominant transmission with high degree of penetrance.
Detection of Urticaria with Food Additives Intolerance by Means of Diet
Authors: Rudzki Edward , Czubalski Krzysztof , Grzywa Zdzislawa
Published: October 2009

A diet free of salicylates, benzoates and azo dyes was applied to 158 patients with chronic urticaria. On the basis of the results of this diet, 50 persons were recognized as ‘sensitive’ to food additives. Psychosomatic examination of the latter patients demonstrated that they do not differ significantly from the remaining ones as regards exacerbations of skin changes by psychological stress. On the other hand, the coexistence of a frustrating situation at the beginning of appearance of skin changes is markedly less frequent in persons ‘sensitive’ to food additives. Patients are described in whom intolerance to food additives occurred together with hypersensitivity to drugs or some kinds of food.
Manifestations cutanées d’une thrombocytémie associée à une myélofibrose chez une patiente psoriasique traitée au PUVA
Authors: Bovet R. , Cech P.
Published: October 2009

Cutaneous manifestations of thrombocythaemia are caused by vascular lesions, either haemorrhagic or thrombotic, affecting above all the microcirculation of the extremities. The authors report a case of thrombocythaemia associated with myelofibrosis discovered by ischaemic lesions on the toes which appeared at the beginning of PUVA therapy for psoriasis. The type of vascular lesions generally depends on the platelet count. In the presence of these cutaneous manifestations, the determination of both platelet counts and functions may orient the diagnosis toward a myeloproliferative syndrome.
Transfer Factor Treatment in Bullous Pemphigoid
Authors: Khan Amanullah , Ayyar Rajeshwari , Michaelson Jerold D. , Weaver Robert E. , Hill N.O.
Published: October 2009

A patient with bullous pemphigoid, not responding to prednisone, had impaired cellular immunity. Transfer factor (TF) was given in doses of 10 U/m2 intramuscularly to improve T cell immunity, at a frequency of 3 times to once a week. Clinical improvement fluctuated with changes in the frequency of TF injections. The skin has been clear of the lesions for the past 9 months. Her T cell functions became normal and serum IgE decreased from 900 U/ml to 270 U/ml. She has received a total of 1,732 U of TF. This report is intended to encourage investigation into T cell functions in patients with bullous pemphigoid and controlled trials of TF in this disease.
Th17 Immunity in Patients with Allergic Asthma
Authors: Zhao Yang , Yang Jiong , Gao Ya-dong , Guo Wei
Published: October 2009

Background: Allergic asthma is an inflammatory disease regulated by the T helper (Th) cells. The Th1/Th2 imbalance has been well documented in the pathogenesis of allergic asthma. Recently, Th17 cells have been found to participate in the development of allergic asthma in animals. However, whether Th17 immunity contributes to the systemic immune responses in allergic asthmatic patients is unclear. Methods: Peripheral blood mononuclear cells were isolated from allergic asthmatics (n = 29) and healthy controls (n = 12). The frequencies of Th1, Th2 and Th17 cells were analyzed by flow cytometry. The related cytokine (IFN-γ, IL-4, IL-17, IL-22, IL-23 and IL-25) concentrations in plasma and culture supernatants were measured by enzyme-linked immunosorbent assay and Luminex. The level of retinoic acid-related orphan receptor γt (RORγt), a key transcription factor controlling Th17 differentiation, was examined by real-time quantitative polymerase chain reaction. Results: The percentages of Th2 and Th17 cells as well as the concentrations of Th2- and Th17-related cytokines were higher in allergic asthmatics than those in healthy controls; some patients were even treated with inhaled glucocorticoid. The percentages of Th17 cells as well as the plasma concentrations of IL-17 and IL-22 tended to increase with the severity of the disease, while the IL-25 level was elevated in mild patients. A parallel elevation of IL-17 and IL-23 concentrations and an increase in RORγt level were found in allergic asthmatics. Conclusion: Our results suggest that besides predominant Th2 immunity, abnormal Th17 immunity may be also involved in the pathogenesis of allergic asthma.
Galectin-9 in Allergic Airway Inflammation and Hyper-Responsiveness in Mice
Authors: Sziksz Erna , Kozma Gergely Tibor , Pállinger Éva , Komlósi Zsolt István , Ádori Csaba , Kovács Lajos , Szebeni Beáta , Rusai Krisztina , Losonczy György , Szabó András , Vannay Ádám
Published: October 2009

Background: Galectin-9 (Gal-9) is a member of the growing family of β-galactoside-binding lectins. Gal-9 is an eosinophil chemoattractant and inducer of Th1 cell apoptosis. These effects suggest its potential role in the pathogenesis of asthma. Our aim was to study the expression of Gal-9 in an ovalbumin (OVA)-induced mouse model of allergic asthma. Methods: To investigate the significance of Gal-9 in allergic inflammation and airway hyperresponsiveness (AHR), a group of BALB/c mice was sensitized and challenged with OVA (GOVA). Another group of animals was allergized with OVA and also treated with dexamethasone (DEX) (GOVA+DEX). The control group (GPBS) received phosphate-buffered saline instead of OVA as placebo. Airway reactivity to intravenous methacholine was assessed. Results: The percentage of Gal-9-positive cells and their intracellular Gal-9 content and Th1/Th2 cytokine levels in the bronchoalveolar lavage (BAL) were determined by flow cytometry. Gal-9 mRNA expression and protein level were measured in the lung tissue by real-time RT-PCR and Western blot. In GOVA mice, airway inflammation and mucus hypersecretion developed. DEX treatment inhibited the main features of experimental asthma. The number of Gal-9-positive lymphocytes, eosinophil and neutrophil granulocytes and the levels of Th2 cytokines were higher in the BAL of GOVA compared to GPBS or GOVA+DEX mice. Moreover, Gal-9 protein level was elevated in the lungs of GOVA mice. Conclusions: These results suggest that Gal-9 plays a role as a mediator contributing to the development of allergic airway inflammation. Gal-9 may serve as a recruiter of eosinophil granulocytes and promoter of Th2 dominance.
Prevalence of Food Allergy among Children in Al-Ain City, United Arab Emirates
Authors: Al-Hammadi S. , Al-Maskari F. , Bernsen R.
Published: October 2009

Background: Food allergy (FA) in children is an important health problem. However, the prevalence of FA in the United Arab Emirates (UAE) has not yet been determined. This cross-sectional study was carried out to assess the prevalence of FA among school children aged 6–9 years in Al-Ain city, UAE. Methods: We used multistage random sampling in order to get a sample of 397 school children whose parents completed a self-administered questionnaire designed to assess the presence or absence of physician diagnosis of FA and other allergic diseases. Results: The study showed that the prevalence of physician-diagnosed FA in children was 8% (95% CI 5.4–10.8%). Eggs, fruits and fish were the main allergies reported. FA was independently related to a family history of FA, to a small sibship size and to a personal history of other atopic diseases. Conclusions: The prevalence of FA in Al-Ain city was 8%. A history of FA in first-degree family members and a small sibship size were associated with a higher risk of FA in children. FA was related to a personal history of other atopic diseases.
The Longest Wheal Diameter Is the Optimal Measurement for the Evaluation of Skin Prick Tests
Authors: Konstantinou George N. , Bousquet Philippe-Jean , Zuberbier Torsten , Papadopoulos Nikolaos G.
Published: October 2009

Background: Mean diameter or longest diameter are the 2 most frequently used parameters for wheal response assessment after skin prick testing (SPT). We aimed to compare these 2 parameters taking as gold standard the surface of the wheal skin response. Patients and Methods: Patients suspected of having an allergic reaction against inhalant allergens have been skin prick tested using the Pan-European GA2LEN SPT panel. Fifteen minutes later, macroscopically evident wheal and flare reactions were marked with a pen and transferred to paper with a transparent scotch tape. Each paper-transferred wheal was scanned with an ordinary scanner, and its surface-corresponding maximum perpendicular diameters and longest diameters were measured using a computer software application for image recognition, developed for this purpose. Correlation coefficients (Spearman’s ρ) between surfaces and respective mean (ρmean) or longest (ρlongest) diameters were calculated and subsequently compared. Results: 1,554 SPTs were performed in 74 patients. In 264, a macroscopically evident wheal and flare response was observed. Both mean and longest diameters correlated significantly with the wheal surfaces. However, ρlongest was statistically significantly larger than ρmean when the surface of the wheal was >17 mm2 (ρlongest > 0.860 vs. ρmean < 0.660; p < 0.05).Such a surface corresponds to a maximum diameter of approximately 7 mm and a mean diameter of approximately 6 mm. Thus, the larger the surface of the wheal, the more appropriate the usage of the longest diameter. Conclusions: The longest wheal diameter alone seems to be a better surrogate marker of the wheal surface in comparison with the mean diameter. In addition, it is easier and faster to measure. Therefore, we propose this as the optimal methodology to evaluate SPTs.
HLA Antigens in Atopic Dermatitis
Authors: Larsen Schultz , Grunnet N. , Vase P.
Published: October 2009

The HLA antigens in a family with atopic dermatitis were studied. All family members with atopic dermatitis had haplotype A2, Bw35, Cw4. It has been recently demonstrated that HLA type Bw35 is found with an increased frequency in atopic dermatitis. There appears to be an inconsistent and weak correlation between atopic dermatitis and HLA-A, HLA-B and HLA-C loci.
Lepromatous Leprosy and Contact Dermatitis
Authors: Jerez J. , Quintanilla E. , Martin-Gil D. , Ayesa C. , Oehling A.
Published: October 2009

The rare association of lepromatous leprosy and allergic contact dermatitis due to chromium in cement was confirmed clinically and biologically in a male patient. The apparent lack of influence of lepromatous leprosy on the development and maintenance of this dermatitis dependent upon cell-mediated immune mechanisms is discussed.
Lymphome épidermotrope type Woringer-Kolopp
Authors: Bourlond A. , Delbrouck-Poot F. , Philippart J.L. , Bourlond-Reinert L.
Published: October 2009

A 46-year-old female, otherwise healthy, developed erythematous, pseudotumoral nodules, mainly on the hands; biopsies led to the diagnosis of Woringer-Kolopp disease. Anti-anergic chemotherapy with levamisole proved hazardous but, possibly, beneficial. Classification into benign localized, fatal generalized and intermediate disease is briefly commented upon. Differential diagnosis and tumor origin are discussed; while the Merkel cell hypothesis has been recently advanced strong analogies and slight discrepancies with mycosis fungoides advocate the T cell lymphoma theory.
Spättyp-Überempfindlichkeit gegenüber Staphylokokkenantigenen bei Meerschweinchen
Authors: Meyer J.C. , Grundmann H.-P. , Weiss H. , Trachsel H.
Published: October 2009

Delayed type hypersensitivity against staphylococcal antigens could be induced in guinea pigs by injecting the animals with a staphylococcal homogenate in Freund’s adjuvant in all four foot pads and the nuchal skin. Maximal skin reactivity, tested intracutaneously, was observed 21 days after sensitization. Highest stimulation of lymph node cells and peripheral blood lymphocytes was also obtained 21 days after sensitization. When comparing cell walls, cell materials (nonsoluble material obtained after the separation of the cell wall fraction) and soluble fraction (obtained after sedimentation of all nonsoluble material, the strongest skin test reactions occurred after testing intracutaneously with the cell wall fraction.
Generalized Eruptive Histiocytoma
Authors: Sohi A.S. , Tiwari V.D. , Subramanian C.S.V. , Chakraborty M.
Published: October 2009

A case of generalized eruptive histiocytoma in a 52-year-old Indian male is described. This is probably the tenth case in the world and the first from this country. Histopathological features are discussed in detail and the literature is reviewed.
Experimental Studies on Phototoxic and Photoallergic Reaction by the Skin Window Technique
Authors: Nishioka Kazue , Fujita Hidesuke
Published: October 2009

The differentiation of photoallergic contact dermatitis by 3,3′, 4′, 5-tetra-chlorosalicylanilide from phototoxic contact dermatitis by 8-MOP in guinea pigs was studied by skin window technique. Based upon the results, it may be concluded that the photoallergic reaction can be differentiated from phototoxic reaction by the appearing pattern of basophilic leukocytes.
Multiple granulomata pyogenica bei Acne vulgaris
Authors: Hagedorn M. , Kirclmer S.
Published: October 2009

Multiple granulomata pyogenica are usually satellites of a primary lesion recently treated unsuccessfully. Disseminated pyogenic granulomas are very uncommon. In our case report, we describe a young man with six granulomata pyogenica over the chest, after treating his acne with tetracycline and vitamin A acid. In the discussion, we include infection, trauma and vitamin A acid as factors which can induce the vascular tumor in the region of a vascular dysplasia.
Is Palmoplantar Keratoderma of Greither’s Type a Separate Nosologic Entity?
Authors: Kansky A. , Arzenšek J.
Published: October 2009

17 patients with palmoplantar keratoderma (PPK) were detected among 48 investigated members of the clan O. 5 of these 17 patients had a well-expressed hyperkeratosis on their knees. In one family hyperkeratosis of the knees was inherited as a dominant feature, but in two other families it was not. The observation was made that the expressivity of the disease was fading: while there were 15 PPK patients among the 25 investigated members in the generations II and III, there were only 2 patients among 22 members in the generations IV and V. In addition to PPK incontinentia pigmenti was diagnosed in two instances and pollex duplex in one. The question of the identity of PPK of Greither’s type is shortly discussed.
Immunological Studies in Psoriasis
Authors: Bedi T.R. , Sehgal S. , Sengupta S. , Kaur S.K. , Aikat B.K.
Published: October 2009

The mean values of serum immunoglobulins A, G, M and D levels in 42 psoriasis patients showed no significant difference from those of control subjects. Analysis of the same sera for the presence of antiglobulin antibodies also yielded negative results. Antinuclear factor could be demonstrated in only 4.8% of the cases. The possibility that serum antiglobulins get drained into the lesions making their detection in the serum difficult, is supported by our preliminary findings of focal deposition in the stratum corneum of immune complexes of IgG, IgM and complement in tissue sections of psoriatic lesions from these patients.
Vitiligo, Autoimmune Hemolytic Anemia and T Lymphocyte Dysfunction: a Mere Coincidence or a New Entity?
Authors: Sidi Y. , David M. , Shohat B. , Feuerman E.J. , Pinkhas J.
Published: October 2009

A patient with vitiligo, autoimmune hemolytic anemia and T lymphocyte dysfunction is described. The question whether these findings are due to a common immunological disorder or a mere coincidence is raised.
Behandlung des Lichen ruber mucosae mit Vitamin-A-Säure-Derivaten
Authors: Scheiber Wiltrud , Plewig Gerd
Published: October 2009

27 patients with lichen planus mucosae or erosive lichen planus mucosae were treated with two vitamin A acid derivatives, 13-cis-retinoic acid or an aromatic retinoid. 20 patients were definitively improved or healed. The treatment was especially effective in erosive lesions of the oral mucous membrane. Side-effects of this treatment are pointed out.