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Article ; Online: Light chain restriction confined to lower portions of cutaneous lymphocytic proliferations: a potential diagnostic pitfall.

Hardin, Justin C / Barrows, Brad / Duff, James I / Wasko, Carina A / Orengo, Ida / Perri, Anthony / Huttenbach, Yve T / Diwan, A H

Journal of cutaneous pathology

2014 Volume 41, Issue 12, Page(s) 978–980

MeSH term(s)	Aged ; Aged, 80 and over ; Diagnosis, Differential ; Female ; Humans ; Immunoglobulin Light Chains/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Lymphoma, B-Cell, Marginal Zone/diagnosis ; Lymphoma, B-Cell, Marginal Zone/immunology ; Lymphoma, B-Cell, Marginal Zone/pathology ; Male ; Skin Neoplasms/immunology ; Skin Neoplasms/pathology
Chemical Substances	Immunoglobulin Light Chains
Language	English
Publishing date	2014-12
Publishing country	United States
Document type	Case Reports ; Letter
ZDB-ID	187078-6
ISSN	1600-0560 ; 0303-6987
ISSN (online)	1600-0560
ISSN	0303-6987
DOI	10.1111/cup.12404
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Article ; Online: Promotion of melanoma growth by the metabolic hormone leptin.

Ellerhorst, Julie A / Diwan, A H / Dang, Shyam M / Uffort, Deon G / Johnson, Marilyn K / Cooke, Carolyn P / Grimm, Elizabeth A

Oncology reports

2010 Volume 23, Issue 4, Page(s) 901–907

Abstract: We have previously shown that melanoma cells proliferate in response to the metabolic hormones TRH and TSH. The objective of the present study was to test the hypothesis that a third metabolic hormone, leptin, serves as a growth factor for melanoma. ... ...

Abstract	We have previously shown that melanoma cells proliferate in response to the metabolic hormones TRH and TSH. The objective of the present study was to test the hypothesis that a third metabolic hormone, leptin, serves as a growth factor for melanoma. Using western blotting, indirect immunofluorescence, and RT-PCR, leptin receptors were found to be expressed by human melanoma cells. In contrast, cultured melanocytes expressed message for the receptor without detectable protein. Melanoma cells responded to treatment with leptin by activating the MAPK pathway and proliferating. Melanoma cells but not melanocytes, also expressed leptin protein, creating a potential autocrine loop. Examination of human melanoma tumors by immunohistochemistry revealed that melanomas and nevi expressed leptin at a high frequency. Melanomas also strongly expressed the leptin receptor, whereas nevi expressed this receptor to a much lesser degree. We conclude that leptin is a melanoma growth factor and that a leptin autocrine-loop may contribute to the uncontrolled proliferation of these cells.
MeSH term(s)	Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins/metabolism ; Leptin/metabolism ; Melanoma/metabolism ; Melanoma/pathology ; Mitogen-Activated Protein Kinases/metabolism ; Nevus/metabolism ; Receptors, Leptin/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/physiology ; Skin Neoplasms/metabolism ; Skin Neoplasms/pathology
Chemical Substances	Intercellular Signaling Peptides and Proteins ; Leptin ; Receptors, Leptin ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2010-03-04
Publishing country	Greece
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or_00000713
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Zs.A 4213: Show issues

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Article: Cutaneous toxoplasmosis: a case of confounding diagnosis.

Lee, S A / Diwan, A H / Cohn, M / Champlin, R / Safdar, A

Bone marrow transplantation

2005 Volume 36, Issue 5, Page(s) 465–466

MeSH term(s)	Adult ; Bone Marrow Transplantation ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/parasitology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Skin Diseases, Parasitic/diagnosis ; Skin Diseases, Parasitic/etiology ; Skin Diseases, Parasitic/pathology ; Toxoplasmosis/diagnosis ; Toxoplasmosis/etiology ; Toxoplasmosis/pathology
Language	English
Publishing date	2005-09
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/sj.bmt.1705079
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Zs.A 2168: Show issues

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Article: Nuchal-type fibroma in two related patients with Gardner's syndrome.

Diwan, A H / Graves, E D / King, J A / Horenstein, M G

The American journal of surgical pathology

2000 Volume 24, Issue 11, Page(s) 1563–1567

Abstract: Nuchal-type fibroma is a distinct subcutaneous and dermal fibrous tissue proliferation that has been previously definitely identified in one patient with Gardner's syndrome and has been possibly present in two others. Gardner's syndrome is an autosomal- ... ...

Abstract	Nuchal-type fibroma is a distinct subcutaneous and dermal fibrous tissue proliferation that has been previously definitely identified in one patient with Gardner's syndrome and has been possibly present in two others. Gardner's syndrome is an autosomal-dominant condition with variable expressivity that comprises epidermoid cysts, fibrous tumors, osteomas, intestinal polyposis, as well as other findings. We report two cases of nuchal-type fibroma presenting in a 13-year-old boy in the right upper back and in his 60-year-old grandfather in the upper chest at the posterior axillary line. Both individuals carried a diagnosis of Gardner's syndrome and neither of them had diabetes. Although the boy has as of now only presented with cutaneous manifestations of Gardner's syndrome, his grandfather has exhibited both cutaneous and intestinal evidence of this syndrome. In addition, the boy's mother and her sister have documented Gardner's syndrome. Light microscopic findings of nuchal-type fibroma from both patients include paucicellular, haphazardly arranged collagen bundles with entrapped adipose tissue. A marked diminution of elastic fibers was noted with Van-Gieson stains. The lesions were diffusely positive for CD34 and contained a few factor XIIIa-positive cells. Electron microscopic analysis revealed no differences between the collagen comprising the nuchal-type fibroma as compared with control dermal collagen obtained from skin away from the tumor. These cases strengthen the view that there is an association between nuchal-type fibroma and Gardner's syndrome.
MeSH term(s)	Adolescent ; Antigens, CD34/analysis ; Female ; Fibroma/chemistry ; Fibroma/etiology ; Fibroma/pathology ; Fluorescent Antibody Technique, Indirect ; Gardner Syndrome/complications ; Gardner Syndrome/metabolism ; Gardner Syndrome/pathology ; Genetic Diseases, Inborn ; Humans ; Male ; Middle Aged ; Neck ; Pedigree ; Soft Tissue Neoplasms/chemistry ; Soft Tissue Neoplasms/etiology ; Soft Tissue Neoplasms/pathology ; Transglutaminases/analysis
Chemical Substances	Antigens, CD34 ; Transglutaminases (EC 2.3.2.13)
Language	English
Publishing date	2000-11
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	752964-8
ISSN	1532-0979 ; 0147-5185
ISSN (online)	1532-0979
ISSN	0147-5185
DOI	10.1097/00000478-200011000-00015
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Zs.A 1356: Show issues

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Article: Cyclic GMP-dependent protein kinase activity in rat pulmonary microvascular endothelial cells.

Diwan, A H / Thompson, W J / Lee, A K / Strada, S J

Biochemical and biophysical research communications

1994 Volume 202, Issue 2, Page(s) 728–735

Abstract: Cyclic GMP-dependent protein kinase (cGPK) activity was determined in rat pulmonary microvascular endothelial cells (RPMVEC) using cGMP-stimulated phosphorylation of BPDEtide and histone F2B substrates in the presence of PKI [peptide inhibitor of cAMP- ... ...

Abstract	Cyclic GMP-dependent protein kinase (cGPK) activity was determined in rat pulmonary microvascular endothelial cells (RPMVEC) using cGMP-stimulated phosphorylation of BPDEtide and histone F2B substrates in the presence of PKI [peptide inhibitor of cAMP-dependent protein kinase (cAPK)]. RPMVEC cGPK activity was localized to the 100,000 x g cytosolic fraction. The EC50 for cGMP activation in the presence of PKI was 0.16 microM and H-89 inhibition under similar conditions showed an IC50 value of 0.16 microM. Anion-exchange chromatography of RPMVEC and rat lung cytosolic fractions showed separation of the cGMP-dependent from the cGMP-independent protein kinase activity and similar elution conductivities. Further, Western blots of RPMVEC active DEAE-Trisacryl fractions showed immunoreactivity using bovine Type I cGPK antiserum. Preliminary studies reveal six potential substrates phosphorylated by cGPK in RPMVEC. These studies describe an endothelial cell (EC) cGMP-receptor, cGPK, in addition to cGMP-activated (Type II) phosphodiesterase (PDE).
MeSH term(s)	Amino Acid Sequence ; Animals ; Anions ; Blotting, Western ; Chromatography, Ion Exchange ; Cyclic GMP/pharmacology ; Cytosol/enzymology ; Endothelium, Vascular/enzymology ; Lung/blood supply ; Microcirculation/enzymology ; Molecular Sequence Data ; Phosphorylation ; Protein Kinase Inhibitors ; Protein Kinases/metabolism ; Rats ; Sodium Chloride ; Substrate Specificity
Chemical Substances	Anions ; Protein Kinase Inhibitors ; Sodium Chloride (451W47IQ8X) ; Protein Kinases (EC 2.7.-) ; Cyclic GMP (H2D2X058MU)
Language	English
Publishing date	1994-07-29
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1006/bbrc.1994.1991
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Zs.A 116: Show issues

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Article: Pulmonary microvascular and macrovascular endothelial cells: differential regulation of Ca2+ and permeability.

Kelly, J J / Moore, T M / Babal, P / Diwan, A H / Stevens, T / Thompson, W J

The American journal of physiology

1998 Volume 274, Issue 5, Page(s) L810–9

Abstract: Cytosolic Ca2+ concentration ([Ca2+]i) plays an important role in control of pulmonary vascular endothelial cell (ECs) barrier function. In this study, we investigated whether thapsigargin- and ionomycin-induced changes in cytosolic Ca2+ induce ... ...

Abstract	Cytosolic Ca2+ concentration ([Ca2+]i) plays an important role in control of pulmonary vascular endothelial cell (ECs) barrier function. In this study, we investigated whether thapsigargin- and ionomycin-induced changes in cytosolic Ca2+ induce permeability in rat pulmonary microvascular (RPMV) versus macrovascular (RPA) ECs. In Transwell cultures, RPMVECs formed a tighter, more restrictive barrier than RPAECs to 12,000-, 72,000-, and 150,000-molecular-weight FITC-labeled dextrans. Thapsigargin (1 microM) produced higher [Ca2+]i levels in RPAECs than in RPMVECs and increased permeability in RPAEC but not in RPMVEC monolayers. Due to the attenuated [Ca2+]i response in RPMVECs, we investigated whether reduced activation of store-operated Ca2+ entry was responsible for the insensitivity to thapsigargin. Addition of the drug in media containing 100 nM extracellular Ca2+ followed by readdition media with 2 mM extracellular Ca2+ increased RPMVEC [Ca2+]i to a level higher than that in RPAECs. Under these conditions, RPMVEC permeability was not increased, suggesting that [Ca2+]i in RPMVECs does not initiate barrier disruption. Also, ionomycin (1.4 microM) did not alter RPMVEC permeability, but the protein phosphatase inhibitor calyculin A (100 nM) induced permeability in RPMVECs. These data indicate that, whereas increased [Ca2+]i promotes permeability in RPAECs, it is not sufficient in RPMVECs, which show an apparent uncoupling of [Ca2+]i signaling pathways or dominant Ca(2+)-independent mechanisms from controlling cellular gap formation and permeability.
MeSH term(s)	Animals ; Calcium/metabolism ; Capillary Permeability/drug effects ; Capillary Permeability/physiology ; Cells, Cultured ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Extracellular Space/metabolism ; Male ; Microcirculation/physiology ; Pulmonary Artery/cytology ; Pulmonary Artery/metabolism ; Pulmonary Circulation/drug effects ; Pulmonary Circulation/physiology ; Rats ; Rats, Sprague-Dawley ; Thapsigargin/pharmacology
Chemical Substances	Thapsigargin (67526-95-8) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	1998
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2948-8
ISSN	0002-9513
ISSN	0002-9513
DOI	10.1152/ajplung.1998.274.5.L810
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Article: Inhibition of serine-threonine protein phosphatases decreases barrier function of rat pulmonary microvascular endothelial cells.

Diwan, A H / Honkanen, R E / Schaeffer, R C / Strada, S J / Thompson, W J

Journal of cellular physiology

1997 Volume 171, Issue 3, Page(s) 259–270

Abstract: The flux of multisized fluorescein-isothiocyanate-labeled hydroxy ethyl starch (FITC-HES) macromolecules was used to assess changes in barrier function of rat pulmonary microvascular endothelial cell (RPMVEC) monolayers exposed to protein phosphatase (PP) ...

Abstract	The flux of multisized fluorescein-isothiocyanate-labeled hydroxy ethyl starch (FITC-HES) macromolecules was used to assess changes in barrier function of rat pulmonary microvascular endothelial cell (RPMVEC) monolayers exposed to protein phosphatase (PP) inhibitors or cGMP analogs and atriopeptin (ANF). Two potent PP inhibitors, calyculin A (CalA) and okadaic acid (OA), increased RPMVEC permeability in a dose- and time-dependent manner, and CalA had a higher intrinsic activity than OA. In contrast, ANF and potent cGMP analogs had no effect on basal RPMVEC permeability. The phosphohistone PP activity contained in RPMVEC sonicates was inhibited by OA with an inhibition profile that suggested at least two components were present, with PP2A accounting for approximately 70% of the OA-inhibitable phosphohistone phosphatase activity. Following separation with heparin-Sepharose chromatography, PP activity exhibited equipotent inhibition by CalA and differential inhibition by OA. Differential inhibition of PP1 and PP2A by OA suggested that PP1 is involved in regulating RPMVEC barrier function. Permeabilized RPMVEC showed increased phosphorylation of several proteins in the presence of phosphatase inhibitors. Treatment with KT 5926, a myosin light chain (MLC) kinase (MLCK) inhibitor, or rolipram, a phosphodiesterase inhibitor, decreased 32P incorporation into immunoprecipitated MLC by CalA and OA. However, this effect did not abolish either the CalA- or OA-induced decrease in the RPMVEC barrier function. Localization of filamentous (F) actin was at the periphery as well as in the cytoplasm and perinuclear region, whereas nonmuscle myosin was seen in the perinuclear region. Neither of these patterns was changed in the presence of CalA. Thus, cGMP does not alter RPMVEC permeability, but inhibition of PP activity results in loss of barrier function by a mechanism independent from MLC phosphorylation.
MeSH term(s)	Animals ; Cyclic GMP/pharmacology ; Endothelium, Vascular/cytology ; Endothelium, Vascular/physiology ; Enzyme Inhibitors/pharmacology ; Intercellular Junctions/drug effects ; Lung/blood supply ; Microcirculation ; Okadaic Acid/pharmacology ; Oxazoles/pharmacology ; Phosphoprotein Phosphatases/antagonists & inhibitors ; Phosphoprotein Phosphatases/physiology ; Rats
Chemical Substances	Enzyme Inhibitors ; Oxazoles ; Okadaic Acid (1W21G5Q4N2) ; calyculin A (7D07U14TK3) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Cyclic GMP (H2D2X058MU)
Language	English
Publishing date	1997-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/(SICI)1097-4652(199706)171:3<259::AID-JCP4>3.0.CO;2-N
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Article ; Online: Phase II trial of imatinib mesylate in patients with metastatic melanoma.

Kim, K B / Eton, O / Davis, D W / Frazier, M L / McConkey, D J / Diwan, A H / Papadopoulos, N E / Bedikian, A Y / Camacho, L H / Ross, M I / Cormier, J N / Gershenwald, J E / Lee, J E / Mansfield, P F / Billings, L A / Ng, C S / Charnsangavej, C / Bar-Eli, M / Johnson, M M /

Murgo, A J / Prieto, V G

British journal of cancer

2008 Volume 99, Issue 5, Page(s) 734–740

Abstract: Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one ...

Abstract	Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Base Sequence ; Benzamides ; DNA Primers ; Disease Progression ; Female ; Humans ; Imatinib Mesylate ; Male ; Melanoma/blood supply ; Melanoma/diagnostic imaging ; Melanoma/drug therapy ; Melanoma/secondary ; Middle Aged ; Piperazines/adverse effects ; Piperazines/therapeutic use ; Positron-Emission Tomography ; Pyrimidines/adverse effects ; Pyrimidines/therapeutic use ; Skin Neoplasms/blood supply ; Skin Neoplasms/diagnostic imaging ; Skin Neoplasms/drug therapy ; Skin Neoplasms/pathology ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Benzamides ; DNA Primers ; Piperazines ; Pyrimidines ; Imatinib Mesylate (8A1O1M485B)
Language	English
Publishing date	2008-08-19
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/sj.bjc.6604482
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