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Cellular and Molecular Biology Volume 14 Number 1 1999
A. Alvarez, J. Lacalle, M. García-Sanz, J. Simón, J. Aréchaga and
S.-H . Br or son, T. Ande rse n, S. Haug, I . Kr ist i ansen, A .
E. Hi lari o: Epigenet ic mod ula ti on of dif fe rent i ati on in C E44
Risstubben, H. Tchou and J. Ulstein: Antigen retrieval on epoxy
teratocarcinoma . 1-9
sections based on tissue infiltration with a moderately increased K. Horie, D. Chen and H. Hoshi: Development of immune complex
amount of a cceler at or to det ect i mmune complex deposits i n trapping: experimental study of lymphoid follicles and germinal centers glomerular tissue . 151-155
newly induced by exogenous stimulants in mouse popliteal lymph T. Kohgo, F. Mezawa, T. Iizuka and M. Shindoh: The enhancing
nodes . 11-21
effect of excess retinol palmitate on induction of odontogenic tumors S.A. Kalamidas and O.B. Kotoulas: The degradation of glycogen in
and inhibitory effect on squamous cell carcinoma of the gingiva in the lysosomes of newborn rat hepatocytes: glycogen-, maltose- and hamsters treated with N-methylnitrosourea .157-163
isomaltose-hydrolyzing acid alpha glucosidase activities in liver . 23-30
B. Peláez, J.L. Blázquez, F.E. Pastor, A. Sánchez and P. Amat:
O. Sandström, J. Mahdavi and M. El-Salhy: Age-related changes in
Lect inhistochemistry and ul trastructure of mi crogl ial r esponse antral endocrine cells in mice . 31-36
to monosodium glutamate-mediated neurotoxicity in the arcuate
nucleus . 165-174
T. Ohmori, S. Asahi, C. Sato, F. Maki, A. Masumoto and K. Okada:
Bcl-2 protein expression and gut neurohormonal polypeptide/amine
production in colorectal carcinomas and tumor-neighboring mucosa,
which closely correlate to the occurrence of tumor . 37-44
A. Castañeyra-Perdomo, M. del M. Pérez-Delgado, E. Carmona-
Calero, H. Pérez González, N. Marrero-Gordillo and R. Ferres-
Y. Su, S. Damjanovski, Y. Shi and Y.-B. Shi: Molecular and cellular
Torr es: Effect of hyper tension and captopril t reatment on the
basis of tissue remodeling during amphibian metamorphosis . 175-183
vasopressin in the rat median eminence and posterior lobe of the Z. Xing, M. Jordana, J. Gauldie and J. Wang: Cytokines and
hypophysis. An immunohistochemical study . 45-49
pulmonary inflammatory and immune diseases . 185-201
M.K. Heatley: Systematic review and meta-analysis in anatomic
demonstration of metallothionein in benign and malignant canine pathology: the value of nuclear DNA content in predicting progression mammary tumours . 51-61
in low grade CIN, the significance of the histological subtype on B. Miskowiak and M. Partyka: Effect of neonatal treatment with MSG
prognosis in cervical carcinoma . 203-215
(Monosodium glutamate) on thyroid of the adult male rats . 63-67
B.S. Mitchell and U. Schumacher : The use of the lectin H e l i x
E. Gómez-Barrena, E. Martínez-Moreno, R. Ballesteros Massó, D.
p o m a t i a agglutinin (HPA) as a prognostic indicator and as a tool in Martínez Pérez and L. Munuera Martínez: Gold chloride technique to
cancer research . 217-226
study articular innervation. A protocol validated through computer- A. Pardo and M. Selman: Proteinase-antiproteinase imbalance in the
assisted colorimetry . 69-79
pathogenesis of Emphysema: The role of metalloproteinases in lung N. Gassler, F. Rastar and M.W. Hentz: Angiogenesis and expression
damage . 227-233
of tenascin after transmural laser revascularization . 81-87
D.S. Askew and F. Xu: New insights into the function of noncoding
J. Nacher, C. Ramírez, J.J. Palop, A. Molowny, J.A. Luis de la
RNA and its potential role in disease pathogenesis . 235-241
Iglesia and C. López-García: Radial glia and cell debris removal
Z. Grozdanovic and H.G. Baumgarten: Nitric oxide synthase in
during lesion-regeneration of the lizard medial cortex . 89-101
skeletal muscle fibers: a signaling component of the dystrophin- J. Nacher, C. Ramírez, J.J. Palop, P. Artal, A. Molowny and C.
glycoprotein complex . 243-256
L ó p e z - G a r c í a : Microglial cells during the lesion-regeneration of the
T.M. Mayhe w, R. Myklebust , A. Whybrow and R. Jenki ns:
lizard medial cortex . 103-117
Epithelial integrity, cell death and cell loss in mammalian small J.M. Monge, J.F. Val-Bernal, L. Buelta, L. García-Castrillo and L.
intestine . 257-267
A s e n s i o : Selective nuclear morphometry as a prognostic factor of
J. Diebold: Molecular genetics of ovarian carcinomas . 269-277
survival in renal cell carcinoma . 119-123
I.O. Baas, R.H. Hruban and G.J.A. Offerhaus: Clinical applications
M. Sali do, J. Larr án, A. López, J. Vilches and J. Aparicio:
of detecting dysfunctional p53 tumor suppressor protein . 279-284
Etoposide sensitivity of human prostatic cancer cell lines PC-3, DU
145 and LNCaP . 125-134
N. Sheibani and W.A. Frazier: Thrombospondin-1, PECAM-1, and
regulation of angiogenesis . 285-294
M. Yamakawa, Y. Imai, M. Dobashi and T. Kasajima: Development
of follicular dendritic cells: A study using short-term bone marrow cell
G. Hübner, C. Alzheimer and S. Werner: Activin: A novel player in
grafting in SCID mice . 135-142
tissue repair processes . 295-304
H. Nakayama, S. Kajikawa, J. Shinozuka, W-P. Su and K. Doi:
D. Sviridov: Intracellular cholesterol trafficking . 305-319
Possible involvement of DNA methylation in 5-azacytidine-induced L.M. Neri, S. Capitani, P. Borgatti and A.M. Martelli: Lipid signaling
neuronal cell apoptosis . 143-150
and cell responses at the nuclear level . 321-335
Published by "Jiménez Godoy, S.A." D.L. MU-33-1986 January 1999
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Cellular and Molecular Biology Volume 14 Number 2 1999
S.M. Albarenque, J. Shinozuka, S. Iwamoto, H. Nakayama and K.
K. Okudela, T. Ito, Y. Kameda, N. Nakamura and H. Kitamura:
Doi: T-2 toxin-induced acute skin lesions in Wistar-derived hypotrichotic
Immunohistochemical analysis for cell proliferation-related protein WBN/ILA-Ht rats . 337-342
expression in small cell carcinoma of the esophagus; a comparative H. Chen, D. Hayakawa, S. Emura, A. Tamada, M. Jamali, Y. Ozawa,
study with small cell carcinoma of the lung and squamous cel l H. Taguchi, R. Yano, N. Ohtake and S. Shoumura: Effects of long-
carcinoma of the esophagus . 479-485
term treatment with ethanol on the ultrastructure of the golden hamster R. Martín, A. Gutiérrez, A. Peñafiel, M. Marín-Padilla and A. de la
parathyroid gland . 343-349
C a l l e : Persistence of Cajal-Retzius cells in the adult human cerebral
cortex. An immunohistochemical study . 487-490
I.T. Said, A.M. Shamsuddin, M.A. Sherief, S.G. Taleb, W.F. Aref and
D. Kumar: Comparison of different techniques for detection of Gal-
GalNAc, an early marker of colonic neoplasia . 351-357
B.J. Desai, H.E. Gruber and E.N. Hanley Jr.: The influence of
Matrigel™ or growth factor reduced Matrigel™ on human intervertebral
R. Todd and D.T.W. Wong: Epidermal growth factor receptor (EGFR)
disc cell growth and proliferation . 359-368
biology and human oral cancer .491-500
S.P. Collin and H.B. Collin: The foveal photoreceptor mosaic in the
K. Djabali: Cytoskeletal proteins connecting intermediate filaments to
pipefish, Corythoichthyes paxtoni (Syngnathidae, Teleostei) . 369-382
cytoplasmic and nuclear periphery . 501-509
C. Ferrer, F. Solano and A. Zuasti: Ultrastructural and biochemical
A. Matsukawa an d M. Yoshi naga: Neutrophil s as a source of
analysis of epidermal xanthophores and dermal chromatophores of the cytokines in inflammation . 511-516
teleost Sparus aurata . 383-390
A.T. Dandjinou, I. Dionne, S. Gravel, C. LeBel, J. Parenteau and
A.M. Safer and A.J. Al-Nughamish: Hepatotoxicity induced by the
R.J. Wellinger: Cyt ological and funct ional aspects of telomere
anti-oxidant food additive, butylated hydroxytoluene (BHT), in rats: An maintenance . 517-524
electron microscopical study . 391-406
P.J. Marie: Cellular and molecular alterations of osteoblasts in human
C. Sarasquete, J.A. Muñoz-Cueto, J.B. Ortiz, F.J. Rodríguez-
disorders of bone formation . 525-538
Gómez, M.T. Dinis and H. Segner: Immunocytochemical distribution of
cytochrome P4501A (CYP1A) in developing gilthead seabream, Sparus
N. Ashizawa, M. Niigaki, N. Hamamoto, M. Niigaki, T. Kaji, T.
aurata . 407-415
Katsube, S. Sato, H. Endoh, K. Hidaka, M. Watanabe and Y.
Kinoshita: The morphological changes of exocrine pancreas in chronic
C. Kaur, J. Singh, S. Moochhala, M.K. Lim, J. Lu and E.A. Ling:
pancreatitis . 539-552
Induction of NADPH diaphorase/nitric oxide synthase in the spinal cordmotor neurons of rats fol owing a single and multiple non-penetrative M. Werner, J. Mueller, A. Walch and H. Höfler: The molecular
blasts . 417-425
pathology of Barrett's esophagus . 553-559
A. Mobasheri: Brefeldin A influences the cell surface abundance and
A.E.H. Merrie, K. Yun, A.M. van Rij and J.L. McCall: Detection and
intracellular pools of low and high ouabain affinity Na+, K+-ATPase α significance of minimal residual disease in colorectal cancer . 561-569
subunit isoforms in articular chondrocytes . 427-438
R.L. Balleine and C.L. Clarke: Expression of the oestrogen responsive
L.K. Malen dowicz, M. Tretjer, R. de Caro, N. Jedrejczak, R.
protein pS2 in human breast cancer . 571-578
Brel i nska, A. M arkowska, G. G . Nussdorf er and M. No wak:
T.M. Chiang: Collagen-platel et interaction: pl atelet non-integri n
Cholecystokinin, acting through the A receptor subtype, stimulates receptors . 579-585
the proliferative activity of adrenocortical cells and thymocytes in the Z. Liu, F.P. Luyten, J. Lammens and J. Dequeker: M o l e c u l a r
rat . 439-443
signaling in bone fracture healing and distraction osteogenesis 587-595
K. Hiramatsu and K. Ohsh im a: Ul trastruct ural locali zati on of
A. M. Dvorak a nd E . S. Morgan : Ri bonucleas e-gold l abel s
ac et yl choli nesterase (AChE ) act i vi ty i n t he chicken Harder ian proteoglycan-containing cytoplasmic granules and ribonucleic acid- gland . 445-451
containing organelles - A survey . 597-626
B.-F. Qian, M. El-Salhy, Å. Danielsson, A. Shalaby and H. Axelsson:
F. F urukawa: Ant inuclear antibody-kerati nocyte i nt eracti ons i n
Changes in intestinal endocrine cells in the mouse after unilateral photosensitive cutaneous lupus erythematosus . 627-633
cervical vagotomy . 453-460
N.A. Athanasou and A. Sabokbar: Human osteoclast ontogeny and
P. Peschke, V. Klein, G. Wolber, E. Friedrich and E.W. Hahn:
pathological bone resorption . 635-647
Morphometric analysis of bromodeoxyuridine distribution and celldensity in the rat Dunning prost ate tumor R3327-AT1 foll owing N. L. Ban ik and D. C. Sh i el ds: A putat i ve role f or calpain i n
treatment with radiation and/or hyperthermia . 461-469
demyelination associated with optic neuritis . 649-656
J. ˘Cejková, J. Zvárová, Z. Andonová and T. Ardan: C o m p a r a t i v e
J. Southgate, P. Harnden and L.K. Trejdosiewicz: C y t o k e r a t i n
histochemical and biochemical studies on acid ß-galactosidase expression patterns in normal and malignant urothelium: a review of the activity in the experimentally injured rabbit cornea and tear fluid using biological and diagnostic implications . 657-664
the sensitive substrate ß-galactoside-4-trifluoromethylumbelliferyl D.L. Crowe and C.F. Shuler: Regulation of tumor cell invasion by
(HFC) . 471-478
extracellular matrix . 665-671
Published by "Jiménez Godoy, S.A." D.L. MU-33-1986 April 1999
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Cellular and Molecular Biology Volume 14 Number 3 1999
X. Ye, A. Scallet and R.I. Carp: Abnormal periodic acid-Schiff (PAS)-positive
Y. Wa ng, N. To kuda, M. Tamechika, N. Hashimoto , M. Yamauch i, H.
substance in the islets of Langerhans, pituitaries and adrenal glands of 139H Kawamura, T. Irifune, M. Choi, A. Awaya, T. Sawada and T. Fukumoto:
scrapie-infected hamsters . 673-678
Vascular and stromal changes in irradiated and recovering rat thymus . 791-796
F. Prignano, L. Domenici, G. Gerlini, N. Pimpinelli and P. Romagnoli:
Human keratinocytes cultured without a feeder layer undergo progressive loss of differentiation markers . 797-803
phosphonate . 679-686
R. Beschorner, H.-P. Horny, U.R. Petruch and E. Kaiserling: F r e q u e n t
G. Mengh i, L. Marc hetti, A.M. Bondi, D. Accili, M.G. Sabbieti and G.
expression of haemopoietic and non-haemopoietic antigens by reactive plasma Materazzi: Double-sided staining with a gold probe and silver enhancement to
cells: an immunohistochemical study using formalin-fixed, paraffin-embedded detect α-amylase and sugar moieties in the mouse salivary glands . 687-695
tissue . 805-812
G. Gheri, G. Russo, P. Cappugi, E. Sgamb ati and S. Gheri Bryk: T h e
T. Na gata, T. Mori ta an d I. Kawah ara : Ra di oa uto grap hic st u die s on
oligosaccharidic component of the glycoconjugates in lichen planus, granuloma radiosulfate incorporation in the digestive organs of mice . 813-820
D. La nge, K. Fun a, A. Ishisa ki, R. Bau er an d U. Wollina : A u t o c r i n e
histochemical study . 697-704
endothelial regulation in brain stem vessels of newborn piglets . 821-825
B-F. Qian, M. El-Salhy, Å. Danielsson, A. Shalaby and H. Axelsson: Effects
of unilateral cervical vagotomy on antral endocrine cells in mouse . 705-709
G. Menghi, A.M. Bondi, L. Marchetti, M.G. Sabbieti, M.G. Gabrielli and G.
L.C. Walker and R.A. Durham: Cerebrovascular amyloidosis: Experimental
Materazzi: Sex-related expression of sialic acid acceptor sugars in the mouse
analysis in vitro and in vivo . 827-837
submandibular gland. Simultaneous visualization by confocal laser scanning
microscopy . 711-717
C. Martinella-Catusse, B. Nawrocki, C. Gilles, P. Birembaut and M. Polette:
Matrix-metalloproteinases in bronchopulmonary carcinomas . 839-843
A. Zimmermann, H. Zimmermann, M. Fellay and J. Reichen: Cells with
P. Schneider, U. Busch, H. Meister, Q. Qasem and P.H. Wünsch: Malignant
morphological and immunohistochemical features of hepatic stellate cells fibrous histiocytoma (MHF). A comparison of MHF in man and animals. A critical (Ito cells) form an extralittoral (extrasinusoidal) compartment in the cirrhotic rat review . 845-860
liver . 719-727
A. Clayton and R. Steadman: ICAM-I interactions in the renal interstitium: A
N. Ishigami, J. Shinozuka, K. Katayama, K. Uetsuka, H. Nakayama and K.
novel activator of fibroblasts during nephritis . 861-870
D o i : Apoptosis in the developing mouse embryos from T-2 toxin-inoculated
dams . 729-733
D. Heymann, G. Pradal and M. Benahmed: Cellular mechanisms of calcium
phosphate ceramic degradation . 871-877
T. Yoshida, H. Matsuda, Y. Hayashida, Y. Gono, T. Nagahara, T. Kawakami,
T. Takenaka, M. Tsukuda and T. Kusakabe: Changes in the distribution of the
L.A. Culp, W-C. Lin and N.R. Kleinman: Tagged tumor cells reveal regulatory
substance P and calcitonin gene-related peptide immunoreactivity nerve fibers steps during earliest stages of tumor progression and micrometastasis 879-886
in the laryngeal mucosa of chronically hypoxic rats . 735-741
G.R. Fanger: Regulation of the MAPK family members: Role of subcellular
K.S. Lips, H. Kaltner, G. Reuter, B. Stierstorfer, F. Sinowatz and H.-J.
localization and architectural organization . 887-894
Gabius: Correspondence of gradual developmental increases of expression of
T. Ito, Y. Noguchi, N. Udaka, H. Kitamura and S. Satoh: Glucose transporter
galectin-reactive glycoconjugates with alterations of the total contents of the two expression in developing fetal lungs and lung neoplasms . 895-904
differentially regulated galectins in chicken intestine and liver as indication for
overlapping functions . 743-760
C. Risco and J.L. Carrascosa: Visualization of viral assembly in the infected
cell . 905-926
F. Afo ns o, M. Pinh o , P. Fe rna nd es , L.R. Mat a an d S. Gul benk ian:
Distribution of vasoactive intestinal peptide and calcitonin gene-related peptide
W. Polkowski, J.J.B. van Lanschot and G.J.A. Offerhaus: Barrett esophagus
immunoreactive nerve fibers and binding sites in the hamster seminal vesicle and cancer: pathogenesis, carcinogenesis, and diagnostic dilemmas . 927-944
during post-natal development . 761-770
A. Zschäbitz, H.-J- Gabius, F.-Y. Zeng, T. Kunt, K.-D. Martens, H. Koepp,
engineering . 945-958
H.-G. Fassbender and E. Stofft: Detection of sarcolectin-specific receptors
D. Escalier: What are the germ cell phenotypes form infertile men telling us
like th e cytokine ma cro ph ag e migratio n i nhibi tory fa ctor in rheuma to id about spermatogenesis? . 959-971
nodules . 771-777
S. Kato, M. Saito, A. Hirano and E. Ohama: Recent advances in research on
U. Wollina, G. Schreiber, M. Görnig, S. Feldrappe, M. Burchert and H-J.
neuropath olo gical a spects of familial amyotrophic later al scl ero sis with Gabius: Sertoli cell expression of galectin-1 and -3 and accessible binding sites
superoxide dismutase 1 gene mutations: Neuronal Lewy body-like hyaline in normal human testis and Sertoli cell only-syndrome . 779-784
inclusions and astrocytic hyaline inclusions . 973-989
E. Fekete, J-P. Timmermans, B.A. Resch and D.W. Scheuermann: Different
R. Rey: The prepubertal testis: a quiescent or a silently active organ? 991-1000
di s tr ibut io n of S-1 00 pr otei n a nd gli al f ib ril lar y ac id ic prot e in ( GFAP)immunoreactive cells and their relations with nitrergic neurons in the human L.A. Cary, D.C. Han and J.-L. Guan: Integrin-mediated signal transduction
fetal small intestine . 785-790
pathways . 1001-1009
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Cellular and Molecular Biology Volume 14 Number 4 1999 (Last issue of this volume) http://www.ehu.es/histol-histopathol
E. Trujillo, D. Alvarez de la Rosa, A. Mobasheri, J. Avila, T. González
D. García-Olmo, D.C. García-Olmo, J. Ontañón, E. Martínez and M.
V a l l e j o: Tumor DNA circulating in the plasma might play a role in
ch ond roc ytes I. Mo rp ho lo gical and func tiona l e xpres sio n of th e metastasis. The hypothesis of the genometastasis .1159-1164
N a+, K+-ATPase α and ß subunit isoforms in healthy and arthritic
chondrocytes . 1011-1022
E. Trujillo, D. Alvarez de la Rosa, A. Mobasheri, T. González, C.M.
Canessa and P. Martín-Vasallo: Sodium transport systems in human
J. Bullerdiek and B. Rommel: Diagnostic and molecular implications of
chondrocytes II. Expression of ENaC, Na+/ K+/ 2 C l- cotransporter and specific chromosomal translocations in mesenchymal tumors . 1165-1173
Na+/H+ exchangers in healthy and arthritic chondrocytes . 1023-1031
H-G. Kim, J. Kassis, J.C. Souto, T. Turner and A. Wells: EGF receptor
F. Jurado, J.M. Bellón, A. Golitsin, M.J. Gimeno, G. Pascual and J.
signaling in prostate morphogenesis and tumorigenesis . 1175-1182
B u j á n : Role of macrophages in myocardial apoptosis following cardiac
K. Nabeshima, T. Inoue, Y. Shimao, H. Kataoka and M. Koono: Cohort
transplant. Influence of immunosuppressive treatment . 1033-1043
migration of carcinoma cells: Differentiated colorectal carcinoma cells J. Cervós Navarro, R.Ch. Kunas, S. Sampaolo and U. Mansmann:
move as coherent cell clusters or sheets . 1183-1197
Heart mitochondria in rats submitted to chronic hypoxia . 1045-1052
M.S. Razzaque and T. Taguchi: The possible role of colligin/HSP47, a
M. García and J. de Juan: Fine structure of the retina of black bass,
collagen-binding protein, in the pathogenesis of human and experimental Micropterus salmoides (Centrarchidae, Teleostei) . 1053-1065
fibrotic diseases . 1199-1212
C. Parrado, F. Carrillo de Albornoz, L. Vidal and I. Pérez de Vargas: A
S-C. Bae and Y. Ito: Regulation mechanisms for the heterodimeric
quantitative investigation of microvascular changes in the thyroid gland transcription factor, PEBP2/CBF . 1213-1221
after infrared (IR) laser radiation . 1067-1071
Y. Kobayashi and M. Kondo: Human megakaryocyte ploidy . 1223-1229
A. Hoc ho l, A. Ma rkow s ka, V. Mene ghell i, N. Jedr zejc za k, M .
S. Barlati, N. Zoppi, A . Copeta, D. Tavian, G. De Petro and M.
Majchrzak, M. Nowak, G.G. Nussdorfer and L.K. Malendowicz: Effects
of neurotensin and bombesin on the secretory and proliferative activity of
Colombi: Quantitative in situ hybridization for the evaluation of gene
regenerating rat adrenal cortex . 1073-1078
expression in asynchronous and synchronized cell cultures and in tissue
sections . 1231-1240
F. Martínez-Soriano, T. Hernández-Gil de Tejada, M. López Bigorra,
S. Ballester Carmona and L. Vollrath: Circadian and seasonal changes
J. Thiele, H.M. Kvasnicka and R. Fischer: Bone marow histopathology
of synaptic bodies in different parts of the rabbit pineal gland . 1079-1091
in chronic myelogenous leukemia (CML)- evaluation of distinctive
features with clinical impact . 1241-1256
A. Navarro, J. Tolivia and M. Alvarez-Uría: Size and degeneration
increase in herring bodies during aging in hamsters . 1093-1099
W.H. Huang and M.H. Zheng: Steroid hormones and bone . 1257-1268
C. Lövdahl, J. Thyberg, B. Cercek, K. Blomgren, P. Dimayuga, B.
P.J. Perrin, A. Lovett-Racke, S.M. Phillips and M.K. Racke: Differential
Kallin and A. Hu ltgårdh -Nilsson: Antisense oligonucleotides to
requirements of naïve and memory T cells for CD28 costimulation in stromelysin mRNA inhibit injury-induced proliferation of arterial smooth autoimmune pathogenesis . 1269-1276
muscle cells .1101-1112
N. Nagahara, T. Ito and M. Minami: Mercaptopyruvate sulfurtransferase
E. Ioachim, D. Assim akopoulos, A.C. Goussia, D. Peschos, A.
as a defense against cyanide toxication: Molecular properties and mode Skevas and N.J. Agnantis: Glycoprotein CD44 expression in benign,
of detoxification . 1277-1286
A. Yoshida, S. Yoshida, T. Ishibashi and H. Inomata: I n t r a o c u l a r
immunohistochemical study including correlation with Rb, p53, Ki-67 and neovascularization . 1287-1294
PCNA . 1113-1118
T. Kobayashi and H. Seguchi: Novel insight into current models of
M.-S. Faussone-Pellegrini, A. Infantino, P. Matini, A. Masin, B. Mayer
NADP H oxi dase regula tion, ass embl y an d lo cal iz ation in hu man and M. Lise: Neuronal anomalies and normal muscle morphology at the
polymorphonuclear leukocytes . 1295-1308
hypomotile iliocecocolonic region of patients affected by idiopathic
chronic constipation . 1119-1134
P. Hiscott, D. Armstrong, M. Batterbury and S. Kaye: Repair in
avascular tissues: fibrosis in the transparent structures of the eye and
A.B. Drakontides, M.J. Danon and S. Levine: Heterotopic neogenesis
thrombospondin 1 . 1309-1320
of skeletal muscle induced in the adult rat diaphragmatic peritoneum:
Ultrastructural and transplantation studies . 1135-1143
Y. Moriwaki, T. Yamamoto and K. Higashino: Enzymes involved in
purine metabolism - A review of histochemical localization and functional
S. Sulkowski and M. Sulkowska: Alveolar cells in cyclophosphamide-
implications . 1321-1340
induced lung injury. II. Pathogenesis of experimental endogenous lipid
pneumonia . 1145-1152
J.M.D. McDonald, J.R. Matyas, J.P. Rattner and J.B. Rattner: Tissue
tra nsf e rs : S ubs t rat es fo r cy to l og y a nd cy to che m is try o f an im a l
S.E. Baldus, F.-G. Hanisch, E. Monaca, U.R. Karsten, T.K. Zirbes, J.
tissues . 1341-1346
Thiele and H.P. Dienes: Immunoreactivity of Thomsem-Friedenreich
(TF) antigen in human neoplasms: The importance of carrier-specific
D.T. Graves, Y. Jiang and A.J. Valente: Regulated expression of MCP-
glycotope expression on MUC1 . 1153-1158
1 by osteoblastic cells in vitro and in vivo . 1347-1354
Published by "Jiménez Godoy, S.A." D.L. MU-33-1986 October 1999
H I S TOLOGY AND
H I S TO PAT H O L O G Y
Cellular and Molecular Biology Volume 15 Number 1 2000
P.E. Fernández, C.G. Barbeito, E.L. Portiansky and E.J. Gimeno:
J. Laborda: The role of the epidermal growth factor-like protein dlk in
Intermediate filament protein expression and sugar moieties in normal cell differentiation . 119-129
canine placenta . 1-6
M. Zaviaˇciˇc and R.J. Ablin: The female prostate and prostate-specific
M. Takekawa, M. Matsuda and S. Ohotubo: Effect of irradiation on
antigen. Immunohistochemical localization, implications of this prostate autogenous bone transplantation in rat parietal bone . 7-19
marker in women and reasons for using the term "prostate" in the
human female . 131-142
J.A. Thliveris, K.T. HayGlass, D. Manchur, E. Rector, A. Begleiter
and J.B. Johnston: Functional status of the immune system after
S.A. Brooks: The involvement of Helix pomatia lectin (HPA) binding N-
chronic administration of 2'-deoxycoformycin in the BB rat . 21-27
acetylgalactosamine glycans in cancer progression . 143-158
S.A. Kalamidas and O.B. Kotoulas: Studies on the breakdown of
A.S. Woolf and P.J.D. Winyard: Gene expression and cell turnover in
glycogen in the lysosomes: The effects of hydrocortisone . 29-35
human renal dysplasia . 159-166
A. Spångéus, S. Forsgren and M. El-Salhy: Does diabetic state
A. Kappeler and C. Mueller: The role of activated cytotoxic T cells in
affect co-localization of peptide YY and enteroglucagon in colonic inflammatory bowel disease . 167-172
endocrine cells? . 37-41
J. Fra nk, H.K. Biesals ki, S. D om ini ci a nd A. Pompella: T h e
J. Tomas, M.A. Lanuza, M. Santafé, M.R. Fenoll-Brunet and N.
visualization of oxidant stress in tissues and isolated cells . 173-184
G a r c i a : Topo logical differences al ong ma mmalian mo tor ne rve
S. Kato: Organ specificity of the structural organization and fine
sprouting . 43-52
study . 185-197
N. Tur unen, P. Pääkkö and Y. Soini: Apoptosis in ga llb ladder
Z. Xing: C urrent understan din g of ma crophage type 1 cytokine
carcinomas and dysplasias, its relation to the expression of caspases responses during intracellular infections . 199-205
3, 6 and 8 a nd apoptosi s re gul ating p rotein s b cl-2, mcl-1 an d R.A. Hess and M. Nakai: Histopathology of the male reproductive
bax . 53-60
system induced by the fungicide benomyl . 207-224
S. Kirkeby and C. Garbarsch: Aging affects different human muscles
N. Johansson and V.-M. Kähäri : Matrix metallopro teinases in
squamous cell carcinoma . 225-237
characteristics of fiber types in human masseter and vastus lateralis
muscles from young adults and the very old . 61-71
D.J. Elliott: Splicing and the single cell . 239-249
M.M. Pérez-Delgado, E. Carmona-Calero, N. Marrero-Gordillo, H.
E.L. Tucker and M. Pignatelli: Catenins and their associated proteins
Pérez-González and A. Castañeyra-Perdomo: Effect of hypertension
in colorectal cancer . 251-260
on the a ngi otensi n II fibres arriving a t the posterior lo be of the hypophysis of the rat. An immunohistochemical study . 73-77
S. Rihet, P. Bellaich, M. Lorenzato, D. Bouttens, P. Bernard, P.
Birembaut and C. Clavel: Human papillomaviruses and DNA ploidy in
expression of mRNA and its protein product: Technical review on anal condylomata acuminata . 79-84
ul tr a s tru c tu r al in si tu h yb ri d iz a ti on a n d it s co mb in at i on w i th
immunohistochemistry . 261-268
U. Wollina, D. Lange, R. Paus, M. Burchert and H.-J. Gabius:
Expression of galectin-1 and -3 and of accessible binding sites during
C. Badid, N. Mounier, A.M.A. Costa and A. Desmoulière: Role of
murine hair cycle . 85-94
myofibroblasts during normal tissue repair and excessive scarring:
Interest of their assessment in nephropathies . 269-280
P.P. Ortiz, R. Sarrat, D. Daret, J. Whyte, A. Torres and J.M. Daniel
A. Negoescu: Apoptosis in cancer: therapeutic implications . 281-297
L a m a z i è r e : Elastin variations implicating in vascular smooth muscle
cells phenotype in human tortuous arteries . 95-100
A.N.A. Monteiro and R.B. Birge: A nuclear function for the tumor
suppressor BRCA1 . 299-307
I. Hatada and T. Mukai: Genomic imprinting and Becwith-Wiedemann
syndrome . 309-312
T. Kanda: Pathological changes of human unmyelinated nerve fibers:
A. Sa cchetti, R . Cicc oc io ppo an d S. A lber ti: The mol ecul ar
a review . 313-324
S.M. Hyder and G.M. Stancel: Regulation of VEGF in the reproductive
mutants . 101-107
tract by sex-steroid hormones . 325-334
G.-L. Jiang and S. Huang: The yin-yang of PR-domain family genes
in tumorigenesis . 109-117
Erratum . 335
Published by "Jiménez Godoy, S.A." D.L. MU-33-1986 January 2000
H I S TOLOGY AND
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Cellular and Molecular Biology Volume 15 Number 2 2000
L. Marchetti, M.G. Gabrielli, G. Materazzi and G. Menghi: C e l l u l a r
M.T. Tseng, S.-A. Chan and S.Z. Guo: A case study of ligation induced
calcification in middle cerebral artery in rat . 483-486
salivary glands. Immunogold approaches at light and electron microscopy J. López, N. Cuesta and M.A. Burrel: Brush-like cells within bronchial
level . 337-346
epithelia of chicken lung (Gallus gallus) . 487-491
O. Sandström and M. El-Salhy: Duodenal endocrine cells in mice with
particular regard to age-induced changes . 347-353
T. Müller: Intraepidermal free nerve fiber endings in the hair les s
s ki n o f t he ra t a s re veal ed by th e zi nc i odi de -os mi um te tr oxi de
F.J. Rodríguez-Gómez, C. Sarasquete and J.A. Muñoz-Cueto: A
technique . 493-498
mo r phol og ica l s tu dy o f th e br a in of Sol e a se ne ga le ns is. I . T h e
telencephalon . 355-364
A. Campos, I.A. Rodriguez, M.C. Sánchez-Quevedo, J.M. García,
O.H. Nieto- Albano an d M.E. Gómez de Ferraris: Mineralization
R. S imak, P. Capo diec i, D.W. Co he n, W. R. Fair , H . Sc he r, J.
of human premolar occlusal fissures. A quantitative histochemical Melamed, M. Drobnjak, W.D. H eston, U. Stix, G. Steiner and C.
microanalysis . 495-502
C o r d o n - C a r d o : Expr ess ion of c- ki t and kit -li gand in benign a nd
malignant prostatic tissues . 365-374
N. Nagy, C. Decaestecker, X. Dong, H. Kaltner, M.-P. Schüring, P.
Ro cm an s, A . Da ngu y, H .- J. Ga bi us , R. K is s a nd I. S a l mon :
L. Jiménez-Reina, R. Cañete, T. Cepeda and G. Bernal: Morphological
Characterization of ligands for galectins, natural galactoside-binding changes to somatotroph cells and in vitro individual GH release, in male rats treated with recombinant human GH . 375-383
expression of calcyclin in thyroid lesions . 503-513
T. Fur uy a, M. Ku bo, A. Uen o, Y. Fujii , T. Baba a nd S . O hno:
His to ch em i ca l stu d y o f a p op tot ic ep i th e lia l c e ll s de p en d ing o n
testosterone in primary cultured rat prostatic tissues . 385-394
E. Lesprit, E. Escudier, G. Roger, V. Prulière, G. Lenoir, Ph. Reinert
and A. Coste: Characterization of inflammatory reaction in upper airways
T. Takizawa and J.M. Robinson: Freeze-fracture cytochemistry: a new
of cystic fibrosis patients . 395-402
fractur e- labeling method for topologic al analysis of biomembrane S. Mai le, B. Zimme rma nn , M. K et tel er and H.-J . Me rk er: T h e
molecules . 515-522
morphology of mesangial cells cultured at high density and in collagen D.V. Kalvakolanu: Interferons and cell growth control . 523-537
gels . 403-414
S. Fais, F. Luciani, M. Logozzi, S. Parlato and F. Lozupone: Linkage
B. Mi´skowiak and M. Partyka: Neonatal treatment witn monosodium
between cell membrane proteins and actin-based cytoskeleton: the glutamate (MS G) : struc ture of the T SH- immun oreactive pituitary cytoskeletal-driven cellular functions . 539-549
cells . 415-419
Y.-L. Chen, H.-W. Wu and M.J. Jiang: Transforming growth factor-ß1
M.L. Hixon, A. Flores, M. Wagner and A. Gualberto: Gain of function
pr operties of mutant p53 proteins at the mitotic spindle cell cycle cholesterol-fed rabbits . 421-428
checkpoint . 551-556
G. Radaelli, C. Dom eneghin i, S. Arrighi, M. Francolini an d F.
A. Rivard and V. Andrés: Vascular smooth muscle cell proliferation in
M a s c a r e l l o : Ultrastructural features of the gut in the white sturgeon,
the pathogenesis of atherosclerotic cardiovascular diseases . 557-571
Acipenser transmontanus . 429-439
K. Agematsu: Memory B cells and CD27 . 573-576
P. Rebuffat, G. Neri, M. Bahçelioglu, L.K. Malendowicz and G.G.
I. Bélanger and J-F. Beaulieu: Tenascin in the developing and adult
N u s s d o r f e r : Prolonged kallikrein inhibition does not affect the basal
human intestine . 577-585
growth and secretory capacity of rat adrenal cortex, but enhancesmi n e ral o- a n d g l u coc o rt i coi d r e sp on se to A C TH a n d ha ndl in g A. Mamoune, V. Durand, P. Le Goff, Y.-L. Pennec, P. Youinou and R.
stress . 441-444
Le Corre: Abnormal distribution of CD45 isoforms expressed by CD4+
and CD8+ T cells in rheumatoid arthritis . 587-591
P. Kanavaros, K. Stefanaki, J. Vlachonikolis, G. Eliopoulos, S.
Ka kolyris, D. Rontogianni, V. Gorgoulis and V. Georg oulias:
M.A. Chernousov and D.J. Carey: Schwann cell extracellular matrix
Expr ession of p53, p21/waf1, bcl-2, bax, Rb and Ki67 proteins in molecules and their receptors . 593-601
Hodgkin's lymphomas . 445-453
P.J. Andres-Barquin, M.-C. Hernandez and M.A. Israel: Id genes in
J. Sanz-Ortega, S.M. Steinberg, E. Moro, M. Saez, J.A. Lopez, E.
nervous system development . 603-618
Sierra, J. Sanz-Esponera and M.J. Merino: Comparative study of tumor
P. Hellman, T. Carling, L. Rask and G. Åkerström: Pathophysiology of
angiogenesis and immunohistochemistry for p53, c-ErbB2, c-myc and primary hyperparathyroidism . 619-627
EGFr as prognostic factors in gastric cancer . 455-462
V. Nehls and W. Hayen: Are hyaluronan receptors involved in three-
K. Honjo and K. Doi: Foreign serum-induced bile duct lesion (BDL) in
dimensional cell migration? . 629-636
athymic BALB/c nude mice . 463-467
S. Cos and E.J. Sánchez-Barceló: Melatonin, experimental basis for a
H. Chen, D. Hayakawa, S. Emura, A. Tamada, Y. Ozawa, H. Taguchi,
possible application in breast cancer prevention and treatment . 637-647
R. Yano and S. Shoumura: Effects of ethanol on the ultrastructure of the
hamster thyroid C-cell . 469-474
B. Kablar and M.A. Rudnicki: Skeletal muscle development in the
mouse embryo . 649-656
F. Sinowatz, D. Sch ams, R. Einspanier, G. Arnold , M. Pfeffer,
L . T em mi m -B ak e r, W . A ms e lg ru b e r a nd J . P le nd l : C ell u lar
L.M. Frago, G. Camarero, S. Cañón, C. Pañeda, C. Sanz, Y. Leon, F.
localization of fibroblast growth factor 2 (FGF-2) in benign prostatic Giraldez and I. Varela-Nieto: Role of diffusible and transcription factors
hyperplasia . 475-481
in inner ear development: implications in regeneration . 657-666
Published by "Jiménez Godoy, S.A." D.L. MU-33-1986 April 2000
H I S TOLOGY AND
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Cellular and Molecular Biology Volume 15 Number 3 2000
A.C. Goussia, E. Ioachim, N.J. Agnantis, M. Mahera and E.V.
V. Krenn, M.M. Souto-Carneiro, H.-J. Kim, C. Berek, P. Starostik, A.
Tsianos: Bcl-2 expression in colorectal tumours. Correlation with p53,
König, H. Har ms and H. K. Müll er -Her melin k: Histopathol ogy
mdm-2, Rb proteins and proliferation indices . 667-672
and molecular pathology of synovial B-lymphocytes in rheumatoid
arthritis . 791-798
E. Nadorfy-López, S.H. Torres, H. Finol, M. Méndez and B. Bello:
Skeletal muscle abnormalities associated with occupational exposure to
W.A. Linke: Stretching molecular springs: elasticity of titin filaments in
mercury vapours . 673-682
vertebrate striated muscle . 799-811
T. Kusakabe, T. Yoshida, H. Matsuda, Y. Yamamoto, Y. Hayashida,
S. Kyo, M. Takakura and M. Inoue: Telomerase activity in cancer as a
T. Kawakami and T. Takenaka: Changes in the immunoreactivity of
diagnostic and therapeutic target . 813-824
substance P and calcitonin gene-related peptide in the laryngeal taste Y. Oda and I. Nakanishi: The distribution of cholinergic neurons in the
buds of chronically hypoxic rats . 683-688
human central nervous system . 825-834
Y. Muro ishi , S. Kasashi ma, I. Nakani shi and Y. O da:
N. Ahuja and J.-P.J. Issa: Aging, methylation and cancer . 835-842
Immunohistochemical and in situ hybr idization studies of cholineacet ylt ransf erase i n lar ge motor neur ons of t he human spinal R.K. Singh and M.L. Varney: IL-8 expression in malignant melanoma:
cord . 689-696
implications in growth and metastasis . 843-849
T. Osanai, M. Yamakawa, A. Suda and Y. Watanabe: Metamorphosed
W- H. Li u and D-G . Wang: Apoptos is r egulat i ng genes in
fibroblasts and their relation to the histogenesis of malignant fibrous neuroendocrine tumors . 851-859
histiocytoma in experimental murine model . 697-705
R.W. Costello, D.B. Jacoby, G.J. Gleich and A.D. Fryer: Eosinophils
K. Katayama, N . Ishi gami, K. Uetsuka, H. Nakayama and K.
and airway nerves in asthma . 861-868
D o i : Ethylni t rosourea ( ENU) -i nduced apoptosis in the rat f et al
F. Alder uccio and B.H. Toh: Immunopathology of autoimmune
tissues . 707-711
gastritis: Lessons from mouse models . 869-879
K. Ohshima and K. Hiramatsu: Distribution of T-cell subsets and
M.E. Lleonart, P. Martin-Duque, R. Sanchez-Prieto, A. Moreno and
immunoglobulin-containing cells in nasal-associated lymphoid tissue S. Ramon y Cajal: Tumor heterogeneity: morphological, molecular and
(NALT) of chickens . 713-720
clinical implications . 881-898
E. Ioachim, A. Charchanti, N.E. Stavropoulos, A. Skopelitou,
D.C. Cara, D. Negrao-Correa and M.M. Teixeira: M e c h a n i s m s
E.D. At hanassi ou and N.J. Agnant i s: I mmunohi st ochemi cal
underlying eosinophil trafficking and their relevance in vivo . 899-920
expression of Retinoblastoma gene product (Rb), p53 protein, MDM2, c-erbB-2, HLA-DR and proliferation indices in human urinary bladder E. Tulchinsky: Fos family members: regulation, structure and role in
carcinoma . 721-727
oncogenic transformation . 921-928
M. Salido, J. Vilches and A. López: Neuropeptides bombesin and
F. Gebhardt, H. Bürger and B. Brandt: Modulation of EGFR gene
calcitonin induce resistance to etoposide induced apoptosis in prostate transcription by secondary structures, a polymorphic repetitive sequence cancer cell lines . 729-738
and mutations - a link between genetics and epigenetics . 929-936
A. Spångeus, O. Suhr and M. El-Salhy: Diabetic state affects the
W. J. Beil , M. Schul z and U. Wefel m eyer : Mast cel l granul e
innervation of gut in an animal model of human type 1 diabetes 739-744
composition and tissue location - a close correlation . 937-946
J. Buján, J.A. Jiménez-Cossio, F. Jurado, M.J. Gimeno, G. Pascual,
W. Li and H. She: The SH2 and SH3 adapter Nck: a two-gene
N. García-Honduvilla, B. Dominguez and J.M. Bellón: Evaluation of
family and a linker between tyrosine kinases and multiple signaling the smooth muscle cell component and apoptosis in the varicose vein networks . 947-955
wall . 745-752
N. Amizuka, J.E. Henderson, J.H. White, A.C. Karaplis, D. Goltzman,
T. Sasaki and H. Ozawa: Recent studies on the biological action of
parathyroid hormone (PTH)-related peptide (PTHrP) and PTH/PTHrP
receptor in cartilage and bone . 957-970
L.S. Caskey, G.N. Fuller, J.M. Bruner, W.K.A. Yung, R.E. Sawaya,
E.C. Holland and W. Zhang: Toward a molecular classification of the
H. Ueda, T. Baba and S. Ohno: Current knowledge of dystrophin and
gliomas: histopathology, molecular genetics, and gene expression dystrophin-associated proteins in the retina . 753-760
profiling . 971-981
M. Rubin, R. Pakula and F.M. Konikoff: Microstructural analysis of
M.A.F. Lopes and C.J. Pfeiffer: Functional morphology of the equine
bile: relevance to cholesterol gallstone pathogenesis . 761-770
pelvic flexure and its role in disease. A review . 983-991
N. Ulfig, F. Neudörf er and J. Bohl: Transient structures of the
A.R. Kitching, S.R. Holdswort h and P.G. Tippi ng: C r e s c e n t i c
human fetal brain: Subplate, thalamic reticular complex, ganglionic glomerul onephi tis - a m anif estat i on of a nephr i togeni c T h1 eminence . 771-790
response? . 993-1003
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Cellular and Molecular Biology Volume 15 Number 4 2000 (Last issue of this volume) http://www.ehu.es/histol-histopathol
J.L. Calvo, J. Boya, A.L. Carbonell and J.E. García-Mauriño: C e l l
A. Zuasti, J.H. Martínez-Liarte, F. Solano and C. Ferrer: M e l a n i z a t i o n
proliferation in the developing rat pineal gland. A bromodeoxyuridine st im ulat ing f act ors in t he i nteg ument of the M ugi l cep hal us a n d immunohistochemical study . 1005-1010
S.A. Kalamidas and O.B. Kotoulas: Glycogen autophagy in newborn rat
hepatocytes . 1011-1018
T. Kusakabe, H. Matsuda, H. Hirakawa, Y. Hayashida, T. Ichikawa,
T. Kawakami and T. Takenaka: Calbindi n D-28k immunoreactive
nerve fibers in the carotid body of normoxic and chronically hypoxic
rats . 1019-1025
K.B. Sandau and B. Brüne: Molecular actions of nitric oxide in mesangial
cells . 1151-1158
I. Martín-Lacave and J.C. Utrilla: Expression of a n e u / c - e r b B - 2 -l i k e
product in neuroendocrine cells of mammals . 1027-1033
R. McCrudden and J.P. Iredale: Liver fibrosis, the hepatic stellate cell
and tissue inhibitors of metalloproteinases . 1159-1168
G. Tuccari, G. Giuffrè, F. Arena and G. Barresi: Immunohistochemical
detection of metallothionein in carcinomatous and normal human gastric
Y. Tanaka: Integrin activation by chemokines: Relevance to inflammatory
mucosa . 1035-1041
adhesion cascade during T cell migration . 1169-1176
Cejková, S. ˇ
Stípek, J. Crkovská and T. Ardan: Changes of superoxide
C. González-Billault and J. Avila: Molecular genetic approaches to
dismutase, catalase and glutathione peroxidase in the corneal epithelium microtubule-associated protein function . 1177-1183
after UVB rays. Histochemical and biochemical study . 1043-1050
C. Millot and J. Dufer: Clinical applications of image cytometry to human
C. Rothman, I. Barshack, A. Gil, I. Goldberg, J. Kopolovic and Z.
tumour analysis . 1185-1200
M a l i k : Potential use of spectral image analysis for t he quantitative
evaluation of estrogen receptors in breast cancer . 1051-1057
C.Y. Koh, L.A. Wel ni ak and W .J. Mur phy: A do pti ve cel l ul ar
I. Takayama, Y. Fujii, N. Terada, T. Baba, Y. Kato, M.A. Fujino and S.
immunotherapy: NK cells and bone marrow transplantation . 1201-1210
O h n o : Topographical difference of cytoskeletal organization in smooth
N. Kyprianou, E.M. Bruckheimer and Y. Guo: Cell proliferation and
muscle cells of rat duodenum revealed by quick-freezing and deep-etching apoptosis in prostate cancer: significance in disease progression and method . 1059-1066
therapy . 1211-1223
T. Kobayashi, V.S. Zinchuk, E. Garcia del Saz, F. Jiang, Y. Yamasaki,
S. Kataoka, T. Okada, S. Tsunawaki and H. Seguchi: S u p p r e s s i v e
M. Poetsch, T. Dittberner, C. Woenckhaus and B. Klei st: Use of
effect of rebamipide, an antiulcer agent, against activation of human in ter phase cyto genet ics in dem onstrat ing specifi c chr omosom al neutrophils exposed to formyl-methionyl-leucyl-phenylalanine . 1067-1076
aberrations in solid tumors - new insights in the pathogenesis of malignant
melanoma and head and neck squamous cell carcinoma . 1225-1231
M. Civallero, S. Barni, R. Nano and E. Capelli: Dendritic cells and
interleukin-2: cytochemical and ultrastructural study . 1077-1085
M.G. Castro, R. Cowen, J. Smith-Arica, J. Williams, S. Ali, S. Windeatt,
R. Cernuda-Cernuda, J.J. Huerta, M. Muñoz Llamosas, M. Álvarez-
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Published by "Jiménez Godoy, S.A." D.L. MU-33-1986 January 2001
FAX: 34-968364150 Title: Human skin reconstruct models: A new applicatin for studies of melanocyte and melanoma biology
Authors: C. Berking and M. Herlyn
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Histol Histopathol (2001) 16: 000-000 Cellular and Molecular Biology Human skin reconstruct models: A new application
for studies of melanocyte and melanoma biology
C. Berking and M. Herlyn
The Wistar Institute, Philadelphia, PA, USA S u m m a r y . Studies of melanocyte and melanoma
similar in vitro and in situ, the culture-induced changes biology using monocultures of cells are limited because due to the two-dimensional growth conditions are of culture-induced morphology changes and ex p r e s s i o n s i g n i ficantly higher in cells from biologically early of genes related to growth, migration, and inva s i o n , lesions, such as radial growth phase (RGP) primary which do not reflect the in situ phenotype of normal melanoma, and from normal skin (Herlyn, 1987).
m e l a n o cytes, nevus cells, or melanoma cells from Melanoma cells can gain genetic abnormalities over time biologically early progression stages. The deve l o p m e n t in culture, for example, deletions of the p16 tumor of organotypic cultures of human skin, in which culture suppressor gene, which are not found in the primary artifacts are greatly diminished and cell-matrix and cell- lesions in situ (Kamb et al., 1994; Guldberg et al., 1997).
cell interactions between different cell types can be Cultured melanocytes and nevus cells are activated for investigated in a three-dimensional system, has opened a expression of genes related to growth, migration, and n ew era for melanoma research. Long-term in vivo invasion, which does not reflect the in situ phenotype of studies, especially important for melanomagenesis and normal resting melanocytes or nevus cells, but rather of melanoma metastasis have become possible through melanoma cells. The culture artifacts of melanocy t e s , grafting of skin reconstructs to immunodef i c i e n t i.e., non-dendritic but bi- to tripolar morphology, laboratory animals. In this rev i ew, principles and r e l a t ively high proliferation rate, and expression of d i fferent methods of skin reconstruction are introduced melanoma-associated antigens, however, can be reverted with focus on the application for pigment cell biology. when melanocytes are co-cultured with ke r a t i n o cy t e s(Valyi-Nagy et al., 1993). The keratinocytes control the Key wor ds: O rganotypic culture, Melanoc y t e ,
phenotypic characteristics of normal melanocytes, which Melanoma, Grafting is mediated through direct cell-cell contacts via the E-cadherin adhesion system (Hsu et al., 1996). The mosta d vanced model to study melanoc y t e - ke r a t i n o cy t e interactions without culture artifacts is the three-dimensional skin reconstruction model. The melanocytes Through the easy access of melanocytic lesions on are located in the basal layer of the engineered epidermis the body surface and marked advances in tissue culture in close contact to multiple ke r a t i n o cytes through their techniques, hundreds of human melanocyte, nevus, and dendritic extensions forming an epidermal melanin unit melanoma cell lines from all different progression stages exactly as in the in vivo situation (Valyi-Nagy et al., h ave become available for experimental studies to a 1990). Recently, different groups have started to greater extent than for any other cancer type. The diverse characterize the biological behavior of melanocytes in and complex biology, immunology, and genetics of skin reconstructs focusing on melanin transfer, response melanoma have put this tumor in the forefront of model to ultraviolet light exposure, and DNA damage systems for studying key issues of modern oncology, (Archambault et al., 1995; Bessou et al., 1996; Cario- such as angiogenesis, apoptosis, drug resistance, Andre et al., 2000). Likewise, melanoma cells have i m m u n o s u r veillance, invasion, and metastasis. While recently been incorporated into skin reconstructs phenotypic and genetic characteristics of cells from demonstrating a striking similarity to the growth and biologically advanced lesions, such as vertical grow t h invasion properties of the original primary lesions from phase (VGP) primary and metastatic melanoma, are very which they were established (Meier et al., 2000).
I nvasion of melanoma cells into the dermis of the Offprint requests to: Dr. Meenhard Herlyn, The Wistar Institute, 3601 r e s p e c t ive human skin equivalent model has been Spruce Street, Philadelphia, PA 19104, USA. Fax: (215) 898-0980: e- o b s e r ved by several groups (Bechetoille et al., 2000; Dekker et al., 2000; Eves et al., 2000) and more detailed Skin reconstruct models and melanoma Table 1. Dermis equivalents. Different materials and methods of dermis reconstruction have been established since the beginning of organotypic skin
De-epidermized dermis Sterilization of human skin without None of repopulation with Regnier et al., 1986; Ghosh et al., 1997 Coprecipitation and homogenization None or inoculation of fibroblasts Boyce et al., 1988 Isolation from rat tail or bovine Embedding of fibroblasts Bell et al., 1981; Smola et al., 1998; Dekker et al., 2000 Polylactic acid, Chemical synthesis of polymers None or inoculation of fibroblasts Cooper et al., 1991 polyglycolic acid, polyglactin studies about the mechanisms and molecules involved in d eveloped (Table 1). They are the supporting structure tumor progression and invasion have just begun and are beneath the stratified epithelium being formed by expected to increase in the near future (Hsu et al., 2000).
ke r a t i n o cytes. Most widely used is de-epidermized Melanoma-skin reconstructs may particularly become an dermis from normal human skin derived from surgery or i nvaluable tool for inve s t i gations of tumor - s t r o m a post mortem (Regnier et al., 1986; Ghosh et al., 1997).
interactions, which have been increasingly recognized to After sterilization by treatment with glycerol, ethy l e n e be essential for tumor cell survival, growth, and invasion. oxide, or gamma irradiation and after removal of the In this review, the different types and techniques of epidermis, the subcutaneous side of the dermis is seeded skin reconstruction are introduced with focus on the with fibroblasts, which re-populate the dermis, and the inclusion of melanocytes and melanoma cells for in vitro opposite, formerly epidermal side is seeded with as well as in vivo studies after transplantation to experimental animals. Other groups, including ours, make dermis from type I collagen mixed with fibroblasts, which remodel the collagen before the seeding of keratinocytes on top.
Figure 1 illustrates schematically the sequential The nomenclature of skin reconstruction is dive r s e .
reconstruction steps of this model. A combination of O rganotypic culture of skin, skin equivalent, skin type I collagen and glycosaminoglycans was established substitute, artificial skin, skin raft culture, skin by Boyce et al. (1988) and synthetic polymers have been reconstruct, epidermal-dermal composite, bioengineered employed as matrices as well (see Table 1). skin, and three-dimensional skin culture are the most In Fig. 2A, a histological example of a 2-week old skin reconstruct is presented. A composite of de-epidermized sterilized dermis cultured on top of a Culture of skin cells
fibroblast-containing type I collagen matrix is shown inFig. 2B. Fibroblasts migrate upwards and populate the The isolation and cultivation of the three major cell de-epidermized dermis, which then is seeded on top with types of normal human skin is well established and keratinocytes. A similar approach was recently described characterized. Stroma-supporting fibroblasts are isolated by Lee et al. (2000). Regardless of which dermis from the dermis, while stratified epithelium-forming equivalent is used, it has become evident that fibroblasts ke r a t i n o cytes and pigment-producing melanocytes are play an important role both for the formation of a mature isolated from the epidermis. Keratinocytes are essential basement membrane (Smola et al., 1998) and for for skin reconstruction and fibroblasts are widely used epidermal differentiation (Lee et al., 2000). for construction of the supporting dermis. The optional In skin reconstructed with de-epidermized dermis, addition of melanocytes to keratinocytes in a ratio of 1:3 an intact basement membrane and a papillary to 1:20 leads to pigmented skin reconstructs. Also morphology of the epidermal-dermal junction zone is Langerhans cells can be successfully integrated into the preserved, whereas in skin reconstructed with fibroblast- reconstruction model, when cord blood-derived CD34+ containing type I collagen matrix, a basement membrane hematopoietic progenitor cells are used (Regnier et al., is being produced by the fibroblasts and ke r a t i n o cy t e s 1997). Although other cells of the skin appendages, during the culture process (Smola et al., 1998) and the vasculature, and immune system can be maintained as epidermal-dermal junction zone stays straight. It is monocultures, inclusion in organotypic culture systems u n k n own, what impact these differences have for has not been established yet. experimental studies. The composition of de-epidermized dermis, which may contain different matrix- Dermis equivalents
bound growth factors, proteases, and cytokines, is notclearly defined yet and differences between indiv i d u a l D i fferent types of dermis equivalents have been donors as well as in the preparation process need to be
Skin reconstruct models and melanoma seeded together onto the dermis equiv a l e n t .
A l t e r n a t ive l y, co-cultures of ke r a t i n o cytes and m e l a n o cytes can be used. In general, approximately5 x 1 05 cells per cm2 dermis equivalent are seeded and U n d i fferentiated ke r a t i n o cytes are used for the left under submerged culture conditions in low calcium, reconstruction of the epidermis equivalent. Melanocytes low serum medium for 3 to 6 days. Subsequent exposure are mixed with ke r a t i n o cytes in a ratio 1:3 to 1:20 and to air induces a differentiation process in thekeratinocytes leading to the formation of multiple layerspiling up on top of each other. The different layers of anormal stratified epithelium are described in Fig. 2A. Amacroscopic view of a pigmented skin reconstruct after2 weeks of culture is demonstrated in Fig. 2C. Themelanocytes are found in the basal layer as single cellssurrounded by the neighboring ke r a t i n o cytes (Fig. 2D).
The melanocytic dendrites extend into the upper layersof the epidermis and pigment is transferred to thekeratinocytes (Archambault et al., 1995). Recently, it hasbeen shown that melanocytes in skin reconstructs protectepidermal basal cells from UVB-induced apoptosis(Cario-Andre et al., 2000). Grafting of skin reconstructs
Skin reconstructs are being used in medicine for covering wounds of patients (Kirsner, 1998). While skinreconstructs in vitro h ave a maximum life-span ofapproximately one month, survival is increased tos everal months or years when grafted to living hosts.
Long-term studies have become possible, which isparticularly of interest for carcinogenesis studies( J avaherian et al., 1998). Fig. 2E shows a pigmentedhuman skin reconstruct on an immunodeficient albinomouse. Histological and immunohistochemical analysesrevealed that: i) host vessels and immune cells infiltratedthe dermis of the grafts, ii) a papillary morphology of theupper dermis developed, iii) the differentiation of theepidermis improved, and iv) the basement membranematured (Fig. 2F). Obviously, not yet defined diffusiblefactors from the host's microenvironment support themorphology and viability of the grafted skinreconstructs. Melanoma in skin reconstructs
When melanoma cells are incorporated into skin reconstructs, a progression stage-related growth patterncan be observed (Bechetoille et al., 2000; Eves et al.,2000; Meier et al., 2000). While cells derived from RGPprimary melanomas or non-aggressive melanoma celllines are found as single cells or clusters throughout theepidermis, cells derived from VGP primary melanomasor aggressive metastatic melanoma cell lines traverse thebasement membrane and invade the dermis equiva l e n t(Fig. 2G,H). Competence for metastasis and long-termg r owth properties may be tested when melanoma-containing skin reconstructs are grafted to living hosts,for example, to immunodeficient mice. Induced expression of invasion-related adhesion Fig. 1. Schematic of the sequential steps of skin reconstruction using
type I collagen with embedded fibroblasts as dermis equivalent.
molecules, such as melanoma cell adhesion molecule
Skin reconstruct models and melanoma Fig. 2. Examples
of human skin
A. Normal human
after 13 days of
x 400. B. Normal
on top of type I
up into the
dermis, after 16
days of culture.
H&E, x 100.
view of a
dermis is made of
type I collagen
D. Normal human
(arrows) in the
basal layer of the
epidermis after 11
days of culture.
20 days after
grafting to a SCID
39 days after
grafting to a SCID
x 100. G. Non-
melanoma in a
stain, x 400). H.
melanoma in a
Collagen IV stain,
Skin reconstruct models and melanoma (Mel-CAM) or the beta 3 integrin subunit of the Bessou S., Surleve-Bazeille J.E., Pain C., Donatien P. and Taieb A.
vitronectin receptor, can convert non-aggressive non- (1996). Ex vivo study of skin phototypes. J. Invest. Dermatol. 107, i nvading melanoma cells into aggressive invading ones as can be demonstrated in skin reconstructs Boyce S.T., Christianson D.J. and Hansbrough J.F. (1988). Structure of ( S a t y a m o o r t hy et al., unpublished data). Thus, a new a collagen-GAG dermal skin substitute optimized for cultured human model for mechanistic studies of human melanoma epidermal keratinocytes. J. Biomed. Mater. Res. 22, 939-957.
biology has become available and is expected to be of Cario-Andre M., Pain C., Gall Y., Ginestar J., Nikaido O. and Taieb A.
increasing use by various research groups. (200 0). Stud ies on ep ide rmis reco nstructed with an d without melanocytes: melanocytes prevent sunburn cell formation but not appearance of DNA damaged cells in fair-skinned caucasians. J.
Invest. Dermatol. 115, 193-199.
O rganotypic culture models as opposed to Cooper M.L., Hansbrough J.F., Spielvogel R.L., Cohen R., Bartel R.L.
monolayer cultures mimic the three-dimensional and Naughton G. (1991). In vivo optimization of a living dermal structure of the respective reconstructed organ. They substitute employing cultured human fibroblasts on a biodegradable combine different orga n - s p e c i fic cell types and va r i o u s polyglycolic acid or polyglactin mesh. Biomaterials 12, 243-248.
d i fferentiation stages of the same cell type with Dekker S.K., van Doorn R., Kempenaar J., Gruis N.A., Vermeer B.J.
s u p p o r t ive matrix. Studies of cell-cell and cell-matrix and Ponec M. (2 000). Skin equivalent: an attractive model to interactions have become possible and culture artifa c t s , evaluate early melanoma metastasis. Melanoma Res. 10, 127-140.
which are common in cells grown in monolayer are Eves P., Layton C., Hedley S., Dawson R.A., Wagner M., Morandini R., absent or diminished in organotypic cultures. The Ghanem G. and Mac Neil S. (2000). Characterization of an in vitro reconstruction of human skin is most advanced and has model of human melanoma invasion based on reconstructed human reached the stage of successful transplantation to skin. Br. J. Dermatol. 142, 210-222.
patients to cover skin defects of ulcers or burns. More Ghosh M.M., Boyce S., Layton C., Freedlander E. and Mac Neil S.
r e c e n t l y, melanocytes and melanoma cells have been (1997). A comparison of methodologies for the preparation of human introduced into the organotypic cultures and their epidermal-dermal composites. Ann. Plast. Surg. 39, 390-404.
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Koprowski H. (1987). Biolo gy of tumor p rogre ssion in human melanocytes. Lab. Invest. 56, 461-474.
Hsu M.Y., Wheelock M.J., Johnson K.R. and Herlyn M. (1996). Shifts in Acknowledgements. We are grateful to Dr. Jonathan Garlick, who provided us with invaluable technical support for the skin reconstruction.
melanomas. J. Invest. Dermatol. Symp. Proc. 1, 188-194.
We also want to thank Emma D eJesus and Ren a Finko for th eir Hsu M.Y., Meier F.E., Nesbit M., Hsu J.Y., Van Belle P., Elder D.E. and Herlyn M. (2000). E-cadherin expression in melanoma cells restores experiments, and Elsa Aglow and Katerina Chruma for their excellent histological work. The studies were supported by National Institutes of expression of invasion-related adhesion receptors. Am. J. Pathol.
Health grants CA 80999, CA 25874, and CA 10815 to M.H. and a 156, 1515-1525.
postdoctoral research fellowship BE 2189/1-1 from the Deutsche Javaherian A., Vaccariello M., Fusenig N.E. and Garlick J.A. (1998).
Forschungs-gemeinschaft to C.B.
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Smola H., Stark H.J., Thiekotter G., Mirancea N., Krieg T. and Fusenig Accepted February 16, 2001
Slovak Academy of Sciences, Institute of Animal Biochemistry and Genetics, 900 28 Ivanka pri Dunaji, Czech and Slovak Federal Republic The assumption is introduced that there are two types of adaptive responses in central neurons in response to signicantly changed circuit activity. Morphological synaptic modications and synapse turnover are thought to be involved in both of these responses, in such a way that in the rst case they are to restore the
OPSO Bidders' Questions and Answers – Medical 1. Page 9 is blank in the RFP. Please confirm that this page was intentionally left blank. Answer: Page was intentionally left blank. 2. "In 2013, OPSO booked approximately 30,795 inmates." In paragraph one the RFP states the current ADP is 2,545. Please explain the drop in ADP from the current ADP of 2,545 and the bidding ADP of 2,000.