bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Characterization of Iridium(III) Complexes Containing (2-Aminoethyl)dimethylphosphine (edmp) or (2-Aminoethyl)diphenylphosphine (edpp). Structures of fac-[Ir(edmp)3]Cl3·5H2O and trans(Cl,Cl),cis(P,P)-[IrCl2(edpp)2]BF4 and Comparisons of Their Properties with Those of the Cobalt(III) and Rhodium(III) Analogs
Authors: Suzuki Takayoshi , Rude Mette , Simonsen Kim P , Morooka Mitsuo , Tanaka Hitoshi , Ohba Shigeru , Galsbøl Frode , Fujita Junnosuke
Published: July 2006

The iridium(III) complexes containing (2-aminoethyl)dimethylphosphine (edmp) or (2-aminoethyl)diphenylphosphine (edpp) were prepared. Crystal structures of fac-[Ir(edmp)3]Cl3·5H2O (2), trans(Cl,Cl),cis(P,P)-[IrCl2(edpp)2]BF4 (3), and Δ(lel3)- and Λ(ob3)-[Ir(R,R-chxn)3](NO3)3·3H2O (4 and 5; chxn = trans-1,2-cyclohexanediamine) were determined by single-crystal X-ray diffraction. Crystal data and final R values are: for 2, FW = 703.7, triclinic, , a = 11.718(2), b = 13.199(1), c = 9.482(1) Å, α = 91.44(1), β = 105.86(1), γ = 90.53(1)°, V = 1410.0(2) Å3, Dx = 1.66 Mg m−3, and Z = 2, R = 0.039 for 5410 reflections. For 3, FW = 808.5, triclinic, , a = 11.465(1), b = 13.694(1), c = 10.049(1) Å, α = 94.764(6), β = 92.197(8), γ = 102.807(8)°, V = 1530.5(2) Å3, Dx = 1.75 Mg m−3, and Z = 2, R = 0.035 for 5978 reflections. For 4, FW = 774.9, hexagonal, P63, a = 13.005(1), c = 10.221(2) Å, V = 1497.1(3) Å3, Dm = 1.71(2), Dx = 1.72 Mg m−3, and Z = 2, R = 0.020 for 1063 reflections. For 5, hexagonal, FW = 774.9, P63, a = 13.359(1), c = 9.848(2) Å, V = 1522.0(3) Å3, Dm = 1.70(2), Dx = 1.69Mg m−3, and Z = 2, R = 0.015 for 1105 reflections. The average Ir–N bond length of 2.167(6) Å in 2 is longer by 0.077(6) Å than those in 4 and 5. The structural data of the corresponding cobalt(III) and rhodium(III) complexes show that the order of the strength of the trans influence of the –PMe2 group in edmp is CoIII < IrIII < RhIII. In 3, the elongation of the metal–nitrogen bond length by the trans influence of the –PPh2 group in edpp is smaller than that of the –PMe2 group in 2, and the elongation is nearly the same as those in the corresponding cobalt(III) and rhodium(III) complexes. The absorption spectra of the two series of complexes, fac-[M(edmp)3]3+ and trans(Cl,Cl),cis(P,P)-[MCl2(edpp)2]+ (M = CoIII, RhIII, and IrIII) are compared and Shimura’s spectrochemical parameters for iridium(III) are discussed.
Suppression of Methemoglobin Formation by Glutathione in a Concentrated Hemoglobin Solution and in a Hemoglobin-Vesicle
Authors: Sakai Hiromi , Takeoka Shinji , Seino Yuriko , Tsuchida Eishun
Published: July 2006

The suppression of methemoglobin (metHb) formation by glutathione (GSH) is difficult because GSH is oxidized not only by the reduction of metHb, but also by oxygen to generate active oxygen species, such as superoxide (O2−•) and hydrogen peroxide (H2O2), which contribute to metHb formation. An effective nonenzymatic reduction of metHb was achieved at a high concentration of Hb (40 wt%, 2.48 × 10−2 M subunits (1 M = 1 mol dm−3)) because the reduction of metHb was accelerated, and at a low partial pressure of oxygen (pO2 = 40 Torr (1 Torr = 133.322 Pa)) because the oxidation of GSH was effectively suppressed. Hb-vesicles, which encapsulate concentrated Hb (40 wt%, 2.48 × 10−2 M subunits), transport oxygen in the blood stream at relatively low pO2 (110 Torr in artery and 40 Torr in venous, 58 Torr in average). The rate of metHb formation in Hb-vesicles was effectively decreased from 3.8 × 10−7 to 1.6 × 10−7 M s−1 by coencapsulating GSH at 58 Torr.
Synthesis of β-Hydroxy Nitriles via Indium-Induced Coupling of Bromoacetonitrile with Carbonyl Compounds
Authors: Araki Shuki , Yamada Masafumi , Butsugan Yasuo
Published: July 2006

The organoindium reagent, derived from indium metal and bromoacetonitrile, reacted with carbonyl compounds in the presence of chlorotrimethylsilane to give, after hydrolysis, β-hydroxy nitriles. The coupling proceeded with high chemoselectivity, though the diastereoselectivity was low.
Friedel–Crafts Transannular Alkylation of Aromatic Compounds with Nonconjugated Cyclic Dienes
Authors: Tateiwa Jun-ichi , Aoki Ikuo , Suama Masakazu , Uemura Sakae
Published: July 2006

Friedel–Crafts transannular alkylation of aromatic compounds with nonconjugated cyclic dienes such as (Z,Z)-1,5-cyclooctadiene (1,5-COD), bicyclo[2.2.1]hepta-2,5-diene (norbornadiene), and 1,4-cyclohexadiene was studied. The five to six isomers of phenylbicyclooctanes were produced in the alkylation of benzene with 1,5-COD in the presence of either Brönsted acid or Lewis acid as the catalyst. The isomer ratios depended on the nature and the amount of catalyst, the reaction time, and the reaction temperature. In the AlCl3-catalyzed reaction of 1,5-COD with toluene it was disclosed that an initial para-rich isomer distribution of the products shifted to a meta-rich one in a prolonged reaction. With norbornadiene a transannular cyclized compounds was obtained, while with 1,4-cyclohexadiene no transannular cyclization was observed.
Conformation of Methyl trans-3-Arylpropenoates in Triplet States and Their Reactivities
Authors: Nakabayashi Kenichi , Ohashi Kyouko , Takamuku Setsuo
Published: July 2006

The photochemical cis–trans isomerization and cycloaddition of methyl trans-3-arylpropenoates in benzene via triplet state were investigated. The results of triplet sensitized cis–trans isomerization clearly indicated that the most stable conformation for methyl 3-phenylpropenoate is a twisted form while methyl 3-(4-biphenylyl)propenoate and methyl 3-(2-naphthyl)propenoate are in the equilibrium states between the trans-planar triplet and twisted form. Photoirradiation of these methyl 3-arylpropenoates in relatively high concentrated benzene solutions gave two isomeric cyclodimers of dimethyl t-3, t-4-diaryl-r-1, c-2-cyclobutanedicarboxylate and dimethyl c-3, t-4-diaryl-r-1, t-2-cyclobutanedicarboxylate as main products. The reactivities of cycloaddition are relatively high where the most stable conformation is twisted form.
Photooxygenation of Diphenanthro[5,4,3-abcd : 5′,4′,3′-jklm]perylene
Authors: Ohshima Shigeru , Uchida Akira , Horiguchi Seiji , Suzuki Atsushi , Fujisawa Shoji , Oonishi Isao
Published: July 2006

The photooxygenation of diphenanthro[5,4,3-abcd : 5′,4′,3′-jklm]perylene (DPP) due to visible-light irradiation was investigated by measuring the absorption spectra and applying semi-empirical molecular orbital methods. It was shown theoretically that molecular oxygen attaches to the central benzene ring of DPP to give an endo-peroxide. The oxygen gradually detaches from the endo-peroxide at room temperature, reproducing DPP. The activation energies for both the reactions of oxygen attachment and detachment were determined based on the temperature dependences of the reaction rates in benzene; 10.0 ± 5.5 kJ mol−1 for the attachment reaction and 83.8 ± 2.5 kJ mol−1 for the detachment reaction.
An Extractive Spectrophotometric Method of Determination of Molybdenum(VI) Using 3-Hydroxy-2-(4-methoxyphenyl)-6-methyl-4H-chromen-4-one
Authors: Dass Rameshwar , Mehta Jaswant Ram
Published: July 2006

3-Hydroxy-2-(4-methoxyphenyl)-6-methyl-4H-chromen-4-one (HL) behaved as a sensitive spectrophotometric reagent for molybdenum(VI). The metal ion formed a yellow complex with the reagent in acetic acid medium. The complex was extractable into 1,2-dichloroethane and the absorbance values remained unchanged for more than one week. Spectral data showed the formation of 1 : 2 species with λmax value at 411 nm. Beer’s law was obeyed over the concentration range of 0—2.3 ppm. The molar absorptivity and Sandell’s sensitivity were calculated to be 5.61 × 104 dm3 mol−1 cm−1 and 0.0017 μg Mo cm−2 respectively, at 411 nm. The effect of as many as 41 cations and 28 anions and complexing agents was studied. Out of these only Sn(II), Ce(IV), citrate, oxalate, disodium dihydrogen ethylenediaminetetraacetate, and hydrogen peroxide interfered seriously. For ten replicate determinations of 1 μg Mo cm−3 the standard deviation was 0.008 with a relative mean error of ±0.09%. The method is simple, selective, precise and rapid. It has been applied satisfactorily to the determination of molybdenum in steels, waters and flue dust samples.
Abnormal Lymphoid Organ Development in Immunodeficient Mutant Mice
Authors: Seymour R. , Sundberg J.P. , Esch H. Hogen
Published: July 2006

Development of the primary and secondary lymphoid organs is a tightly controlled process. These tissues are highly organized to maximize efficiency of the immune response. Spontaneous and targeted mutations in laboratory mice have led to better understanding of the molecular interactions and signaling pathways essential to the development and organization of lymphoid tissues, and the functional consequences of loss or disruption of the normal structures. on the basis of studies of mutations in mice and other species, it has been determined that a wild-type allele of the Foxnl gene is required for normal thymic development and function. The Tlx1, Bapx1, Tcf21, Wt1 and Dh genes are essential for development of the spleen, while mutations of Nkx2-3, Lta, Ltb, Ltbr, Map3k14, Relb, Tnf, Tnfrsf1a, Cxcl13, Blr1 (Cxcr5), or cpdm genes result in disruption of normal splenic microarchitecture. The requirements for organized lymph nodes vary according to anatomic location, but most rely on Id2 (Idb2) and Rorc, in addition to lymphotoxins and Tnfrsf1 1a, Tnfsf11, Relb, Map3k14, Cxcl13, and Blr1 genes. Development of Peyer's patches is dependent on Id2 and Rorc genes, lymphotoxins, and Relb, Map3k14, Il7r, and cpdm genes. Less is known about the requirements for nasal-associated lymphoid tissues (NALT), but Id2 is a requirement. Here we review abnormalities of lymphoid organ development in immunodeficient mutant mice, including spontaneous and targeted mutations of Id2, Rorc, Tnf, Tnfrsf1a, Lta, Ltb, Ltbr, Tnfrsf11a, Tnfsf11, Relb, Map3k14, IL7r, Blr1, and Cxcl13 genes.
The Expression of p63 and Cytokeratin 5 in Mixed Tumors of the Canine Mammary Gland Provides New Insights into the Histogenesis of These Neoplasms
Authors: Ramalho L. N. Z. , Ribeiro-Silva A. , Cassali G. D. , Zucoloto S.
Published: July 2006

Cytokeratin 5 and p63 have been described as basal and myoepithelial cell markers in human breast. Mixed tumors of the canine mammary gland have been associated with a myoepithelial origin. Cytokeratin 5 expression has not been evaluated in these tumors. We investigated the relation between cytokeratin 5 and p63 double-immunohistochemical expression in 23 mixed tumors of the canine mammary gland (10 benign mixed tumors and 13 carcinomas arising from benign mixed tumors) and their origin. Cytokeratin 5 and p63 co-expression was observed in myoepithelial cells of benign mixed tumors, as well as in squamous differentiation of carcinoma arising from benign mixed tumors. Though a few interstitial spindle cells of the mesenchymal components expressed both p63 and cytokeratin 5, the basal epithelial cells were labeled only by cytokeratin 5. The co-expression of p63 and cytokeratin 5 in myoepithelial cells and squamous differentiation suggest that, like in human breast, cytokeratin 5 can also be considered a myoepithelial- and squamous-cell differentiating marker in canine tumors. The presence of some interstitial spindle cells stained for p63 and cytokeratin 5 might be associated with a myoepithelial origin of the mesenchymal component of mixed tumors of the canine mammary gland. Moreover, contrary to p63, basal epithelial cells were labeled by cytokeratin 5, indicating that cytokeratin 5 may not represent an exclusive myoepithelial cell marker but also a basal epithelial cell marker in canine mixed tumors. According to these data, basal epithelial cells may be related to the origin of the epithelial component of mixed tumors of the canine mammary gland.
Truncated Gamma-Glutamyl Carboxylase in Rambouillet Sheep
Authors: Johnson J. S. , Laegreid W. S. , Basaraba R. J. , Baker D. C.
Published: July 2006

A flock of Rambouillet sheep was examined because of increased lamb mortality due to ineffective hemostasis at parturition. Decreased activities of coagulation factors II, VII, IX, and X, and severely reduced hepatic γ-glutamyl carboxylase activity with adequate vitamin K 2,3 epoxide reductase activity was determined.1,21 Parenteral vitamin K1 supplementation did not improve vitamin K-dependent coagulation factor activities in 3 affected lambs. Affected lamb γ-glutamyl carboxylase deoxyribonucleic acid was sequenced, and 4 single nucleotide polymorphisms (SNPs 2-5) of the γ-glutamyl carboxylase gene were identified. Single nucleotide polymorphism-4 results in an arginine to stop codon (UGA) substitution, which prematurely terminates the peptide at residue 686 (R686Stop). This genotype (GATT/GATT) has a strong association with the coagulopathy observed in clinically affected lambs, P < 0.001. The frequency of SNP-3 in exon 11 (R486H) within the MARC 1.1 database is high in the US sheep population overall. Gamma-glutamyl carboxylase activity in hepatic microsomes from a SNP-3 homozygous lamb lacking the SNP-4 mutation (GACC/GACC) was similar to control sheep homozygous for arginine at 486 and also lacking SNP-4 (TGCC/TGCC), indicating that the R486H does not measurably impact γ-glutamyl carboxylase activity. The remaining two SNPs (2 and 5) are located within non-coding intron sequences. These 4 SNPs allowed for determining the genotype associated with the observed fatal coagulopathy. Screening for the premature truncation (SNP-4) based on the presence of a Bbv I restriction site in clinically normal lambs but not in the homozygous affected lambs allows for detection of the heterozygous state (GATT/GACC), because carrier animals are clinically normal.
Disseminated Encephalitozoonosis in Captive, Juvenile, Cotton-top (Saguinus oedipus) and Neonatal Emperor (Saguinus imperator) Tamarins in North America
Authors: Juan-Sallés C. , Garner M. M. , Didier E. S. , Serrato S. , Acevedo L. D. , Ramos-Vara J. A. , Nordhausen R. W. , Bowers L. C. , Parás A.
Published: July 2006

Disseminated encephalitozoonosis was diagnosed in 2 sibling, juvenile, cotton-top tamarins ( Saguinus oedipus) and 3 sibling, neonatal, emperor tamarins (S. imperator) by use of histologic examination, histochemical analysis, electron microscopy, and polymerase chain reaction (PCR) analysis with nucleotide sequencing. All tamarins were captive born at zoos in North America and died with no premonitory signs of disease. The main pathologic findings were myocarditis (4/5), hepatitis (3/5), interstitial pneumonia (3/5), skeletal myositis (3/5), meningoencephalitis (2/5), adrenalitis (2/5), tubulointerstitial nephritis (1/5), myelitis (1/5), sympathetic ganglioneuritis (1/5), and retinitis (1/5). Central nervous system lesions were the most prominent findings in cotton-top tamarins. The inflammation was predominantly lymphocytic and suppurative in cotton-top tamarins, whereas emperor tamarins had granulomatous or lymphoplasmacytic lesions. Intralesional periodic acid-Schiff-, gram-, or acid-fast (or all 3)-positive, oval-to-elliptical shaped organisms were found in 1 cotton-top and the 3 emperor tamarins. By electron microscopy, these organisms were consistent with microsporidia of the genus Encephalitozoon. E. cuniculi genotype III was detected by PCR analysis and sequencing in paraffin-embedded brain, lung, and bone marrow specimens from the cotton-top tamarins. Although PCR results were negative for one of the emperor tamarins, their dam was seropositive for E. cuniculi by ELISA and Western blot immunodetection. These findings and recent reports of encephalitozoonosis in tamarins in Europe suggest that E. cuniculi infection may be an emerging disease in callitrichids, causing high neonatal and juvenile mortality in some colonies. The death of 2 less than 1-day-old emperor tamarins from a seropositive dam supports the likelihood of vertical transmission in some of the cases reported here.
Vascular Lesions in Nine Göttingen Minipigs with Thrombocytopenic Purpura Syndrome
Authors: Maratea K. A. , Snyder P. W. , Stevenson G. W.
Published: July 2006

Tissues from 9 Göttingen minipigs, aged 7 weeks to 1 year, with clinically diagnosed thrombocytopenic purpura syndrome were examined microscopically. All pigs had a history of spontaneous cutaneous purpura that was generally accompanied by disseminated visceral hemorrhages. Hematologic abnormalities included anemia (8 out of 9 pigs) and thrombocytopenia (7 out of 9 pigs), with platelet counts consistently below 20,000/μ. Microscopically, degenerative vascular lesions with morphologic features of arteriosclerosis were present in all 9 pigs. Vascular lesions affected small- to medium-sized muscular arteries and arterioles in various organs and extraparenchymal tissues; vessels of the renal pelvis and coronary arteries were consistently involved. Microscopic lesions in small- to medium-sized muscular arteries consisted of neointimal proliferation, medial thickening, luminal stenosis, thrombosis, disruption and fragmentation of the internal elastic lamina, necrosis of the tunica media, and medial deposits of myxoid matrix material. Microscopic lesions in arterioles included concentric laminar thickening of vessel walls (onion-skin pattern), endothelial cell hypertrophy, smooth muscle cell vacuolation, necrosis of the tunica media, thrombosis, and partial to complete luminal stenosis. Arteritis and/or periarteritis were also noted in 4 out of 9 pigs. Additional microscopic lesions included membranoproliferative glomerulonephritis (3 out of 9), myocardial microinfarcts (4 out of 7), renal interstitial fibrosis (2 out of 9), extramedullary hematopoiesis (6 out of 9), and intracapillary hyaline thrombi (2 out of 9). Degenerative vascular lesions have not been previously described in Göttingen minipigs with thrombocytopenic purpura syndrome. The etiopathogenesis of both the vascular lesions and thrombocytopenic purpura syndrome is currently unknown.
Neurotropism of Highly Pathogenic Avian Influenza Virus A/Chicken/Indonesia/2003 (H5N1) in Experimentally Infected Pigeons (Columbia livia f. domestica)
Authors: Klopfleisch R. , Werner O. , Mundt E. , Harder T. , Teifke J. P.
Published: July 2006

This investigation assessed the susceptibility of experimentally infected pigeons to the highly pathogenic avian influenza virus (HPAIV) H5N1 that caused recent outbreaks of avian influenza in birds and humans in several countries of Asia. For this purpose 14 pigeons were infected ocularly and nasally with 108 EID50 and clinical signs were recorded and compared with five chickens infected simultaneously as positive controls. The chickens demonstrated anorexia, depression, and 100% mortality within 2 days postinoculation. Three of the pigeons died after a history of depression and severe neurological signs consisting of paresis to paralysis, mild enteric hemorrhage, resulting in a mortality of 21%. Gross lesions in these pigeons were mild and inconsistent. Occasionally subcutaneous hyperemia and hemorrhage and cerebral malacia were observed. Microscopic lesions and detection of viral antigen were confined to the central nervous system of these pigeons. In the cerebrum and to a minor extent in the brain stem a lymphohistiocytic meningoencephalitis with disseminated neuronal and glial cell necrosis, perivascular cuffing, glial nodules, and in one bird focally extensive liquefactive necrosis could be observed. The remaining nine pigeons showed neither clinical signs nor gross or histological lesions associated with avian influenza, although seroconversion against H5 indicated that they had been infected. These results confirm that pigeons are susceptible to HPAIV A/chicken/Indonesia/2003 (H5N1) and that the disease is associated with the neurotropism of this virus. Although sentinel chickens and most pigeons did not develop disease, further experiments have to elucidate whether or not Columbiformes are involved in transmission and spread of highly pathogenic avian influenza.
Hyperplastic and Neoplastic Lesions of the Mammary Gland in Macaques
Authors: Wood C. E. , Usborne A. L. , Starost M. F. , Tarara R. P. , Hill L. R. , Wilkinson L. M. , Geisinger K. R. , Feiste E. A. , Cline J. M.
Published: July 2006

Macaques provide an important animal model for the study of hormonal agents and their effects on risk biomarkers for breast cancer. A common criticism of this model is that spontaneous breast cancer has rarely been described in these animals. In this report, we characterize 35 mammary gland lesions ranging from ductal hyperplasia to carcinoma in situ and invasive ductal carcinoma in cynomolgus and rhesus macaques. Based on a retrospective analysis, we estimated the lifetime incidence of mammary gland neoplasia in aged female macaques to be about 6%. Hyperplastic lesions (n = 19) occurred segmentally along ducts and included such features as columnar alteration, micropapillary atypia, and fibroadenomatous change. in situ carcinomas (n = 8) included solid, comedo, cribriform, and micropapillary elements, encompassing 4 of the major architectural patterns seen in human lesions. invasive ductal carcinomas (n = 8) were generally solid, with prominent central necrosis and mineralization, often on a background of micropapillary ductal hyperplasia and in situ carcinoma. Cytologic changes of invasive lesions included increased mitoses, nuclear pleomorphism, extensive microinvasion, and stromal desmoplasia. Axillary lymph-node metastases were confirmed in 5 of the 8 invasive carcinomas. on immunohistochemistry, intraductal and invasive carcinomas had increased Ki67/MIB1 and HER2 expression and selective loss of estrogen and progesterone receptors. These findings suggest that breast cancer is an underreported lesion in macaques and highlight unique morphologic and molecular similarities in breast cancer between human and macaque species.
Histologic and Immunohistochemical Characterization of Spontaneous Pituitary Adenomas in Fourteen Cynomolgus Macaques (Macaca fascicularis)
Authors: Remick A. K. , Wood C. E. , Cann J. A. , Gee M. K. , Feiste E. A. , Kock N. D. , Cline J. M.
Published: July 2006

Pituitary adenomas were identified in 14 of 491 (2.9%) cynomolgus macaques evaluated from 1994 to 2004. Cases included male (8) and female (6) cynomolgus macaques ranging from 18 to 32 years of age. Seven of the pituitary adenomas caused gross enlargement of the pituitary gland that was visible on postmortem examination, whereas the remaining 7 were multifocal microadenomas identified on histologic examination. A total of 35 adenomas were identified in the 14 macaques, 6 of which were being treated for diabetes mellitus. Mean (± SD) pituitary weight was 0.31 ±.42 g, compared with 0.07 ±.02 g for 430 historical control animals (P < 0.0001). Immunohistochemical staining for follicle-stimulating hormone, luteinizing hormone, prolactin, human growth hormone, thyroid-stimulating hormone, and adrenocorticotropic hormone was applied to pituitary tissue from all cases. Immunostaining revealed 22 of 35 (62.9%) lactotroph adenomas, 5 of 35 (14.3%) plurihormonal cell adenomas, 3 of35 (8.6%) corticotroph adenomas, 2 of35 (5.7%) null cell adenomas, 1 of 35 (2.9%) somatotroph adenomas, 1 of 35 (2.9%) mixed corticotroph-somatotroph adenomas, 1 of 35 (2.9%) mixed lactotroph-corticotroph adenomas, 0 of 35 gonadotroph adenomas, and 0 of 35 thyrotroph adenomas. This study represents the first extensive retrospective case series performed to evaluate the histologic and immunohistochemical characteristics of pituitary adenomas in cynomolgus macaques. our findings indicated that macaque pituitary adenomas frequently had mixed histologic appearance and hormone expression, and that, similar to human pituitary adenomas, prolactin-secreting neoplasms were the most prevalent type.
Macrophages and Giant Cell Proliferation Associated with Bone Protein Synthesis and Calcification in the Trachea and Bronchi of Rabbits Intoxicated with Solanum glaucophyllum
Authors: Barros S. S. , Soares M. P. , Gimeno E. J.
Published: July 2006

A histopathologic, immunohistochemical, and ultrastructural study of the trachea and the bronchi of 6 rabbits experimentally intoxicated with the calcinogenic plant Solanum glaucophyllum was performed. Histologically, infiltration of the mucosa and the submucosa of the trachea and the bronchi by macrophages, multinucleated giant cells, a few lymphocytes and mast cells, and calcium deposits in the basal lamina of the epithelium and in elastic fibers were observed. Expression of osteocalcin, osteonectin, and osteopontin was detected in the mucosa, lamina propria, and epithelium. Electron microscopic study of the corresponding areas showed numerous macrophages in the process of fusion to form multinucleated giant cells, activated mesenchymal cells, and calcium precipitation in the basal lamina of epithelium and in elastic fibers. It is suggested that the high levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the plant induces macrophage proliferation, multinucleated giant-cell formation, mesenchymal cell activation, bone-protein synthesis, and calcification. In addition, the synthesis of 1,25(OH)2D3 by local macrophages may have contributed to the calcification.
Pathology of Fatal Highly Pathogenic H5N1 Avian Influenza Virus Infection in Large-billed Crows (Corvus macrorhynchos) during the 2004 Outbreak in Japan
Authors: Tanimura N. , Tsukamoto K. , Okamatsu M. , Mase M. , Imada T. , Nakamura K. , Kubo M. , Yamaguchi S. , Irishio W. , Hayashi M. , Nakai T. , Yamauchi A. , Nishimura M. , Imai K.
Published: July 2006

Highly pathogenic H5N1 avian influenza viruses were isolated in 9 large-billed crows that died in Kyoto and Osaka prefectures in Japan from March to April in 2004. We studied 3 of the 9 crows using standard histologic methods, immunohistochemistry, and virus isolation. The most prominent lesions were gross patchy areas of reddish discoloration in the pancreas. The consistent histologic lesions included severe multifocal necrotizing pancreatitis, focal degeneration and necrosis of neuron and glial cells in the central nervous system, and focal degeneration of cardiac myocytes. All of these tissues contained immunohistochemically positive influenza viral antigens. The virus was isolated from the brain, lung, heart, liver, spleen, and kidney of the crows examined. Thus we concluded that highly pathogenic avian influenza virus was associated with clinical disease, severe pathologic changes, and death in the 3 crows.
Pulmonary Arteriopathy and Idiopathic Pulmonary Arterial Hypertension in Six Dogs
Authors: Zabka T. S. , Campbell F. E. , Wilson D. W.
Published: July 2006

Pulmonary arteriopathy (PA) is the pathologic hallmark in human medicine of diffuse constrictive (medial and intimal remodeling) or multifocal complex (plexiform and dilatative lesions) arterial lesions, or both, that lead to irreversible obliteration of the arterial lumen. Clinically, PA leads to pulmonary arterial hypertension (PAH), of which idiopathic (IPAH) is one of the 5 subsets, and ultimately, to right-sided heart failure (RHF). Clinical and pathologic findings from 6 dogs with diagnosis of IPAH and PA were reviewed. These dogs were of various pure (5/6, 83%) and mixed (1/6, 17%) breeding, 5 months to 9 years (mean 5.2 years) old, and predominantly female (4/6, 67%) and reproductively intact (4/6, 67%). Doppler echocardiography ( n = 5) indicated increased pulmonary arterial pressures during systole (70-135 mm Hg, mean 98 mm Hg) and diastole (35-80 mm Hg, mean 58 mm Hg). All 6 dogs had right ventricular pressure overload, right ventricular eccentric hypertrophy, and RHF. Histologic examination confirmed the clinical diagnosis of IPAH in all dogs, revealing PA characterized by 1 of the 4 main human histologic subsets: 1) isolated medial hypertrophy (1/6, 17%); 2) medial hypertrophy-intimal thickening without the plexiform lesion (1/6, 17%); 3) medial hypertrophyintimal thickening concurrent with the plexiform lesion, which often was regionally clustered and situated near branching points of the respiratory artery, the poststenotic dilatation lesion, and vasculitis (4/6, 66%); and 4) isolated arteritis (1/6, 17%). Ancillary lesions similar to those in humans also complicated the PA (5/6, 83%). The complex lesions and ancillary exudative alveolitis seemed to be important indicators of severe, likely rapidly progressive and fatal, IPAH.
Hereditary Hydrocephalus in Laboratory-reared Golden Hamsters (Mesocricetus auratus)
Authors: Edwards J. F. , Gebhardt-Henrich S. , Fischer K. , Hauzenberger A. , Konar M. , Steiger A.
Published: July 2006

A colony of golden hamsters had an ongoing problem with hydrocephalus. In an attempt to clear the colony of the problem, new breeders from another supplier had been purchased. At termination of a behavioral study, the brain was collected from 35 animals (four of which had died with hydrocephalus during the study) and was examined macroscopically and by light microscopy. Although no animals manifested obvious behavioral changes, 31 of 35 (88.6%, 13/15 males and 18/20 females in control and manipulated groups) had hydrocephalus. Twenty-five animals had macroscopically identifiable hydrocephalus, and six had hydrocephalus identified microscopically. Neither teratogenic concentrations of metals nor mycotoxins were detected in tissues or food, and sera from breeders tested negative for antibodies to Sendai virus, reovirus 3, and lymphocytic choriomeningitis virus. Trial matings of breeders expected to produce hydrocephalic offspring resulted in affected offspring, and mating of breeders expected to produce normal offspring resulted in normal or less-affected offspring. Hydrocephalus was confirmed retrospectively in some breeders. Hereditary hydrocephalus appears to be widespread in hamster stocks in Central Europe. Affected animals do not manifest signs of disease and usually die without obvious premonitory signs. Despite severe hydrocephalus, the animals can breed, and animal handlers do not identify motor deficits or abnormal behavioral activity. This entity is unlike the previously described, hereditary hydrocephalus of hamsters that is phenotypically identifiable and usually is lethal before they attain breeding age.
Neuropathologic Study of Experimental Classical Swine Fever
Authors: Gómez-Villamandos J. C. , de Leániz I. García , Núñez A. , Salguero F. J. , Ruiz-Villamor E. , Romero-Trevejo J. L. , Sánchez-Cordón P. J.
Published: July 2006

The aim of this study was to report on the lesions occurring in the central nervous system (CNS) during experimental classical swine fever (CSF) to clarify the spatial and chronologic distribution of the lesions and virus antigen in the CNS. To learn more about the pathogenetic mechanisms of the lesions during CSF in the CNS and to investigate the role of the virus in these mechanisms, cellular infiltrates and infected cells have been characterized. Twenty-eight pigs were inoculated with the virulent CSF virus isolate Alfort 187 and slaughtered from 2 to 15 postinoculation days; 4 animals of similar background served as a control group. Immunohistochemistry, electron microscopy, and the transferase-mediated deoxyuridine triphosphate nick-end labeling method were used to detect viral antigens and apoptosis. The results showed the presence of nonpurulent meningoencephalitis, occasional microhemorrhages, and apoptosis of the lymphocytes forming the perivascular and interstitital infiltrate in swine with CSF. Macrophages appeared to display little involvement in CNS lesions. The infected cells observed at the early stage of disease were lymphocytes and microglial cells in the rostral portion of the telencephalon, with infection of these cells in other areas in the next stages. The relationship between these lesions and the presence of viral antigen varied according to the type of lesion: hemorrhages were not associated with the presence of antigen in endothelial cells, but infiltrate-cell apoptosis was temporally and spacially associated to viral infection. However, the link between viral infection and the presence of cell infiltrate was far from clear.
Equine Herpesvirus 2-Associated Granulomatous Dermatitis in a Horse
Authors: Sledge D. G. , Miller D. L. , Styer E. L. , Hydrick H. A. , Baldwin C. A.
Published: July 2006

Granulomatous dermatitis in horses has been linked to many etiologies, including various parasites, fungi, and bacteria. Idiopathic forms of granulomatous inflammation-producing diseases, some of which are localized to the skin, also have been reported in horses. Herein we describe a case of recurrent equine granulomatous skin disease characterized by intranuclear viral inclusions within macrophages and giant cells. The histologic changes were primarily noted in the deep dermis and included multifocal to coalescing areas of necrosis marked by histiocytic cell infiltration and presence of giant cells. Electron microscopic examination revealed intranuclear and intracytoplasmic viral particles consistent with herpesvirus. Sequence results of the polymerase chain reaction product were consistent with equine herpesvirus 2, adding another possible etiology to the list of differentials in cases of equine granulomatous skin disease.
Uterine Myxoid Leiomyosarcoma with Widespread Metastases in a Cat
Authors: Cooper T. K. , Ronnett B. M. , Ruben D. S. , Zink M. C.
Published: July 2006

A 10-year-old domestic shorthair cat was spayed to remove bilateral ovarian masses and an enlarged uterus. Both ovaries were effaced by large, irregular, firm, glistening, white cystic masses filled with clear viscous fluid. The uterine lumen was filled with copious amounts of clear viscous fluid, and the uterus contained multiple, firm, glistening, white nodules. Histologic examination revealed an invasive spindle cell neoplasm with features of malignancy, and extensive hypocellular areas containing an alcian blue-positive myxoid matrix. Tumor cells expressed caldesmon, α-smooth muscle actin, and estrogen receptor but were negative for desmin. The animal was euthanized 1 month later because of suspected local tumor recurrence. At necropsy, the abdominal cavity contained 120 ml of mucoid ascites; multiple tumor nodules were present in the abdominal and thoracic cavities. The clinical behavior and gross, microscopic, and immunohistochemical findings established a diagnosis of myxoid leiomyosarcoma.
Neuronal Ceroid Lipofuscinosis in a Vietnamese Pot-bellied Pig (Sus scrofa)
Authors: Cesta M. F. , Mozzachio K. , Little P. B. , Olby N. J. , Sills R. C. , Brown T. T.
Published: July 2006

The neuronal ceroid ipofuscinoses (NCL) are a group of heritable, neurodegenerative, storage diseases, typically with an autosomal recessive mode of inheritance. Cytoplasmic accumulation of storage material in cells of the nervous system and, variably in other tissues, characterizes NCL. NCL has been reported in many animal species, but to the authors' knowledge, this is the first report of the disease in a pig. Blindness and seizures are common clinical signs of disease, neither of which was a feature in this pig. The lesions were restricted to the central nervous system, which was diffusely affected, with the most severe lesions in the hippocampus, cerebral cortex, and cerebellum. The histologic lesions included neuronal loss and gliosis, which contributed to mild cerebrocortical and cerebellar atrophy and accumulation of autofluorescent storage material in neurons and glial cells. The storage material had morphologic, histologic, and ultrastructural properties typical of NCL.
Malignant Mixed Müllerian Tumor in a Rabbit (Oryctolagus cuniculus): Case Report with Immunohistochemistry
Authors: Goto M. , Nomura Y. , Une Y. , Goldschmidt M. H.
Published: July 2006

A rabbit ( Oryctolagus cuniculus) with a homologous malignant mixed müllerian tumor (MMMT) of the uterus with decidualization in the sarcomatous components is described. On histologic examination, the neoplasm was characterized by a carcinomatous and a sarcomatous component with invasion of the myometrium. The epithelial component was a well-differentiated carcinoma, and the nonepithelial component contained large amounts of intracytoplasmic glycogen. The changes in stromal cells were morphologically similar to changes usually found in decidual cells in the pregnant uterus or in deciduosarcomas in rabbits. Results of immunohistochemical analysis indicated that the epithelial components stained positive with cytokeratin (CK7, AE1/3) and the decidual-stromal cells stained positive for vimentin, but did not stain with α-SMA, actin, and desmin. This case fulfills all the criteria of an MMMT in having a carcinomatous and a sarcomatous component, but differs from cases of MMMT in women in that the sarcomatous component had decidualized. To the authors' knowledge, this is the first report of a malignant mixed müllerian tumor in rabbits.
Gastric Adenocarcinoma in a Horse with Portal Vein Metastasis and Thrombosis: A Novel Cause of Hepatic Encephalopathy
Authors: Patton K. M. , Peek S. F. , Valentine B. A.
Published: July 2006

A 17-year-old Quarter horse mare was referred to Cornell University for postmortem examination after 72 hours of encephalopathy that consisted of depression, mania, and blindness. A plasma sample and cerebral spinal fluid demonstrated hyperammonemia. Gross necropsy examination findings included the following: mild icterus, a transmural mass in the glandular portion of the gastric fundus, multiple masses throughout the liver, and a large tumor thrombus in the portal vein. Microscopically, the gastric mass, hepatic masses, and portal vein thrombus were composed of similar neoplastic epithelial cells that formed variably sized acini and branching cords separated by a dense desmoplastic stroma. Throughout the cerebral frontal cortex were numerous Alzheimer type II astrocytes. Hepatic encephalopathy was caused by gastric adenocarcinoma, with metastasis to the liver and the portal vein. The clinical and pathologic lesions from this unique case, as well as hyperammonemia and portal vein thrombosis in the pathogenesis of hepatic encephalopathy, are discussed.
Metastasizing Oral Squamous Cell Carcinoma in an Aged Pig
Authors: Kleinschmidt S. , Puff C. , Baumgärtner W.
Published: July 2006

A 10-year-old, female, pot-bellied pig (Sus scrofa) experienced a 3-month history of reduced appetite, dysphagia, and weight loss. Clinical examination revealed a mass in the left part of the oral cavity extending from the hard to the soft palate. At necropsy, a firm, white, poorly demarcated ulcerated mass at the left hard and soft palate with metastases to the left retropharyngeal lymph node and the lung was observed. Additional findings included a uterine adenocarcinoma, a hepatocellular adenoma, and nodular hyperplasias in spleen and adrenal glands. Histologically, the poorly demarcated, infiltrative growing oral mass consisted of islands, cords, and single epithelial cells with moderate squamous differentiation. Cells were strongly positive for cytokeratin by immunohistochemistry. Similar cells were found in the left retropharyngeal lymph node and the lung. The present findings represent the first report of a metastasizing oral squamous cell carcinoma in a pig.
Ureteral Fibroepithelial Polyp in an Owl Monkey (Aotus nancymae)
Authors: Gozalo A. S. , Hoffmann V. J. , Lambert L. E.
Published: July 2006

Ureteral fibroepithelial polyps are benign mesodermal tumors in humans that occur predominantly in the proximal ureter. During a routine necropsy of a wild-caught, research naïve, adult, male, Aotus nancymae, the left ureter just distal to the renal pelvis contained a pedunculated, lobulated neoplasm with a narrow stalk at the base projecting into the lumen. The left renal pelvis was found to be mildly dilated. The histologic characteristics of the ureteral mass were consistent with a fibroepithelial polyp. To our knowledge, this is the first report describing a ureteral fibroepithelial polyp in a nonhuman primate.
Hemangiopericytoma in the Eyelid of a Horse
Authors: Serena A. , Joiner K. S. , Schumacher J.
Published: July 2006

Hemangiopericytoma (HP) is a well-recognized neoplasm arising from vascular pericytes that has been reported only in the dog and man. In this study, we describe a 14-year-old female Arabian horse that was presented for surgical excision of a 2-cm-diameter expansile subcuticular mass in the right lower eyelid. Histologically, the mass consisted of loosely arranged interlacing streams and storiform bundles of spindle cells that often formed distinct whorls around a central capillary and bundles of collagen (Antoni A-like pattern). Immunohistochemical analysis revealed strong diffuse cytoplasmic immunoreactivity for vimentin and focal immunoreactivity for smooth muscle actin, whereas neoplastic cells did not stain for Factor VIII-related antigen, Glial fibrillary acidic protein (GFAP), or S100. On the basis of histomorphology and immunohistochemical reactivity, the present tumor was diagnosed as HP. To our knowledge, this is the first report describing a HP in a horse.
Myopathy with Central Cores in a Foal
Authors: Paciello O. , Pasolini M. P. , Navas L. , Russo V. , Papparella S.
Published: July 2006

Central core disease is a nonprogressive or slowly progressive congenital myopathy with a variable degree of hypotonia and axial and proximal muscle weakness that is histologically characterized by areas devoid of oxidative enzyme activity, resulting from an absence or low numbers of mitochondria in these regions (central core). A 10-month-old, male, pony foal was examined because of stiff gait, marked contractures of the distal portion of the limbs, flexion deformities of the hooves, and moderate hypotonia that had been present from birth. The foal had increased creatine kinase (282 U/ liter; reference interval 10-135 U/liter), lactate dehydrogenase (1,188 U/liter; reference interval 150–450 U/liter), and aspartate transaminase (377 U/liter; reference interval <290 U/liter) activities, suggesting muscle disease. Muscle biopsy was performed. In cytochrome oxidase-, succinate dehydrogenase-, and reduced nicotinamide adenine dinucleotide tetrazolium reductase-reacted sections, the dominant morphologic feature was the absence of oxidative enzyme activity in the cores. By use of immunohistochemical technique with a monoclonal antibody against desmin, the cores were clearly delineated and a desmin network was present within the cores. Ultrastructurally, the core areas were characterized by preserved sarcomeres with irregular Z-lines, with some streaming or zigzag appearance and abnormal sarcoplasmic reticulum profiles and T-tubules. Lack of mitochrondria within central cores was observed. Diagnosis of myopathy with central cores was made.
Immunochemistry of Lysosomal Storage Disorders
Authors: Parkinson-Lawrence Emma , Fuller Maria , Hopwood John J , Meikle Peter J , Brooks Doug A
Published: July 2006

Background: Lysosomal storage disorders are a group of genetic diseases, each with a broad spectrum of clinical presentation that ranges from attenuated to severe. The immunochemical analysis of patient samples is aimed at several key aspects of patient management, including early detection of the disorder, prediction of clinical severity, determining the most appropriate therapeutic regimen, and monitoring of patients on therapy.

Methods: In this study, we review the current and emerging technology available to achieve these assessments.

Results: Immune assays have direct practical application for the early detection, diagnosis and prognosis of lysosomal storage disorder patients. Multiplexing of these assays may provide a platform to allow newborn screening for multiple lysosomal storage disorders.

Conclusions: We have reviewed the immunochemical techniques available for the analysis of lysosomal storage disorder patient samples and advise that these may be used in conjunction with other technologies for effective patient management.
Standards for Plasma and Serum Proteomics in Early Cancer Detection: A Needs Assessment Report from the National Institute of Standards and Technology-National Cancer Institute Standards, Methods, Assays, Reagents and Technologies Workshop, August 18–19, 2005
Authors: Barker Peter E , Wagner Paul D , Stein Stephen E , Bunk David M , Srivastava Sudhir , Omenn Gilbert S
Published: July 2006

NIST and the National Cancer Institute cosponsored a workshop on August 18–19, 2005, to examine needs for reference materials for early cancer detection. This meeting focused on standards, methods, assays, reagents, and technologies. Needs for plasma and serum proteomics, DNA methylation, and specimen reference collections were discussed, and recommendations from participants were solicited. This report summarizes the discussion and recommendations for proteomics reference materials.
Cell-Free Plasma DNA as a Novel Marker of Aseptic Inflammation Severity Related to Exercise Overtraining
Authors: Fatouros Ioannis G , Destouni Aspasia , Margonis Konstantinos , Jamurtas Athanasios Z , Vrettou Christina , Kouretas Dimitrios , Mastorakos George , Mitrakou Asimina , Taxildaris Kiriakos , Kanavakis Emmanouel , Papassotiriou Ioannis
Published: July 2006

Background: Circulating free plasma DNA is implicated in conditions associated with tissue injury, including exercise-induced inflammation, and thus is a potential marker for athletic overtraining.

Methods: We measured free plasma DNA along with C-reactive protein (CRP), creatine kinase (CK), and uric acid (UA) in 17 recreationally trained men participating in a 12-week resistance training regimen (8 resistance multi-joint exercises selected to stress the entire musculature: bench press, squat, leg press, snatch, hang clean, dead lifts, barbell arm curls, and rowing), consisting of 4 training periods (t1, t2, t3, and t4).

Results: Plasma DNA concentrations increased markedly after t1, t2, and t3 and returned to baseline after t4. There were substantial differences between t2 and t1 and between t3 and t2 plasma DNA concentrations. CRP increased by 300% after t2 and by 400% after t3 (there was no difference between t2 and t3 CRP values) compared with baseline (t0). CK increased only after t3. UA increased after t2 and t3, with a greater increase after t3.

Conclusions: This study demonstrates that, after chronic excessive resistance exercise, plasma DNA concentrations increase in proportion to training load, suggesting that plasma DNA may be a sensitive marker for overtraining-induced inflammation.
Use of Frozen Sera for FT4 Standardization: Investigation by Equilibrium Dialysis Combined with Isotope Dilution-Mass Spectrometry and Immunoassay
Authors: Van Uytfanghe Katleen , Stöckl Dietmar , Ross H Alec , Thienpont Linda M
Published: July 2006

Background: Serum-free thyroxine (FT4) testing is recommended for diagnosis or monitoring of thyroid dysfunction, particularly in cases of hormone binding abnormalities. However, the poor intermethod agreement among commercial FT4 assays suggests a need for standardization with a hierarchically higher measurement procedure. To that purpose, we applied equilibrium dialysis (ED) in combination with isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-tandem MS).

Methods: After ED, we collected dialysate into tubes containing [13C6]-T4 for ID and [13C9]-T4 as carrier, purified the samples by solid-phase extraction, and analyzed them with LC/tandem MS. We evaluated the procedure’s analytical performance and tested its suitability for measurement of hypo-, eu-, and hyperthyroid serum FT4 concentrations. We conducted a pilot method comparison study with 3 commercial assays to investigate whether frozen sera could be used for the purpose of FT4 standardization.

Results: The within-run, between-run, and total CVs (inclusive ED) were 3.7%, 4.2%, and 5.6%, respectively (17.7 pmol/L; n = 20). The mean accuracy, estimated from recovery experiments with dialysate and dialysis buffer supplemented at 8.7, 18.7, and 33.5 pmol/L, and from analysis of certified sera gravimetrically diluted to 9.8, 19.2, and 34.8 pmol/L, was 98.0% to 102.8%. The procedure’s limit of detection and limit of quantification were 0.5 and 1.3 pmol/L, respectively. The method comparison demonstrated the suitability of the selected sera for standardization of FT4 assays and confirmed the lack of assay comparability.

Conclusions: We demonstrated that the described ED-ID-LC/tandem MS procedure and the selected type of sera qualify for standardization of FT4 measurements.