bluuebunny/crossref_metadata_2025 huggingface dataset:
Cutaneous Vascular Neoplasia in 15 Cats: Clinical, Morphologic, and Immunohistochemical Studies
Authors: Miller M. A. , Ramos J. A. , Kreeger J. M.
Published: March 2010

Seven cases of cutaneous hemangioma and nine of cutaneous hemangiosarcoma were diagnosed from biopsy specimens of 15 Domestic Shorthairs of 5,091 cats that were examined by necropsy or biopsy during the 5-year period from 1 January 1986 through 31 December 1990. All but three cats were male. Tumor cells of both hemangiomas and hemangiosarcomas were immunoreactive for factor VIII-related antigen and for vimentin by the avidin biotin peroxidase complex method. In cats with a median age of 10 years, hemangiomas occurred in skin with pigmented hair in six of seven cases without apparent site predilection. These solitary tumors did not recur after excision although one cat (No. 3) subsequently developed cutaneous hemangiosarcoma at another site. Seven of nine hemangiosarcomas occurred in dermis and subcutis of the head, usually on the pinna. All five hemangiosarcomas of the head, for which cutaneous pigmentation could be determined, occurred in unpigmented skin. Cats with hemangiosarcoma had a median age of 12.5 years at the time of diagnosis. Metastasis has not been documented, but hemangiosarcoma has recurred, from 1 month to 2 years after excision, in 6/7 cats that were studied.
A Pathologic and Bacteriologic Study on Otitis Media in Swine
Authors: Shimada A. , Adachi T. , Umemura T. , Kohno K. , Sakaguchi Y. , Itakura C.
Published: March 2010

A pathologic and bacteriologic study on otitis media in swine was performed on 237 swine, ranging in age from 1 day to 1 year. These 237 swine from eight selected farms were slaughtered due to unfavorable prognosis associated with clinical signs of illness. One hundred sixty-three (68.8%) of the 237 swine were found to be affected with otitis, though only a few swine showed clinical signs characteristic of the disease. One hundred fifty-one (63.7%), 53 (22.4%), and 39 (16.5%) had lesions in the middle, external, and internal ear, respectively. Of the 151 cases with otitis media, bilateral and unilateral infection accounted for 114 (75.5%) and 37 (24.5%), respectively. Only 5/53 swine with otitis externa and 6/39 swine with otitis interna failed to show otitis media. All swine with infection in the tympanic cavity had inflammatory lesions in the auditory tube. Examination of the swine grouped by age revealed that, regardless of age, incidence of otitis media was 50–70%. In swine younger than 1 month old, otitis media tended to center on the auditory tube, where a mild infiltration of neutrophils into the mucous membrane was frequent. Thereafter, otitis media increased in degree and extent with age. Forty (26.5%) of the 151 swine affected with otitis media were accompanied by a substantial amount of inflammatory exudate in the tympanic cavity and bulla. Purulent exudate was found in 20/40 (50%) swine. Severe otitis media prevailed in swine between 1 and 4 months of age, showing inspissation of a suppurative exudate in the tympanic cavity and lysis of the underlying osseous wall of the tympanic bulla with subsequent fibrosis. Microorganisms, such as Pasteurella multocida, coryneform group E, and Actinomyces pyogenes, were the prominent isolates from the exudate in the tympanic cavity or in the tympanic bulla of the 19 swine examined. Most cases of otitis externa and interna (the latter infection frequently [22/23] extended to the brain) were associated with severe otitis media. Based on these results, otitis media prevails from the early stages of life and occurs first as an acute inflammation in the auditory tube, and then extends to the other components of the ear and the brain.
A Survey of Epithelial Odontogenic Tumors and Cysts in Dogs and Cats
Authors: Poulet F. M. , Valentine B. A. , Summers B. A.
Published: March 2010

A retrospective histologic study of 12 canine and eight feline epithelial odontogenic tumors and cysts was conducted from oral masses ( n = 3,917) obtained between 1980 and 1990. No sex or breed predilection was identified. Ameloblastoma was observed in two dogs (case Nos. 1, 2) 6 and 8 months of age. Calcifying epithelial odontogenic tumors were seen in a dog (case No. 3) and in two cats (case Nos. 4, 5) between 8 and 16 years of age. Ameloblastic fibroma (or fibroameloblastoma) was observed in cats (case Nos. 6–10) only. Inductive fibroameloblastoma was observed in four cats (case Nos. 6–9) up to 1 year of age, whereas ameloblastic fibroma was seen in a 14-year-old cat (case No. 10). A single ameloblastic odontoma was identified in a 20-month-old dog (case No. 11). Two complex odontomas occurred in a 6-month-old (case No. 12) and a 4-year-old (case No. 13) dog. Odontogenic cysts were identified in five dogs (case Nos. 14–18) aged 4.5 months to 16 years and in a 1-year-old cat (case No. 19) and have not been previously reported in these species. These cysts were lined by a stratified epithelium reminiscent of the appearance of ameloblastic epithelium. An odontogenic keratocyst with prominent central parakeratotic keratinization was identified in one 9-year-old female dog (case No. 20). Almost all epithelial odontogenic tumors were circumscribed, benign tumors that warranted a good prognosis for survival, although local recurrence may have followed (or may follow) incomplete excision. Calcifying epithelial odontogenic tumors may be locally invasive. Of six odontogenic cysts (case Nos. 14–19), two (case Nos. 15, 18) gave rise to basi-squamous carcinomas. The classification and behavior of epithelial odontogenic tumors and cysts in human beings, dogs, and cats are discussed.
Hematologic and Bone Marrow Changes after Short- and Long-term Administration of Two Recombinant Bovine Granulocyte Colony-stimulating Factors
Authors: Cullor J. S. , Smith W. , Zinkl J. G. , Dellinger J. D. , Boone T.
Published: March 2010

Colony-stimulating factors are a category of glycoproteins that are instrumental in the regulation of hematopoiesis and inflammation. This investigation documented the clinical bone marrow and peripheral blood responses to short-term and long-term administration of a recombinant bovine granulocyte colony-stimulating factor (rb-GCSF) and an analog, where the cysteine at position 17 was substituted with a serine (rb-GCSF ser17). The colony-stimulating factors produced the expected changes in the hematologic findings of the bovine subjects in the study, and there was a cell-specific response to the compounds. The sustained neutrophilia in the long-term study indicates that the bovine species can tolerate the administration of recombinant forms of bovine GCSF for extended periods of time without detectable adverse side effects. The neutrophils from the short-term study revealed no apparent fluctuation, either as enhanced or reduced capability to reduce nitro blue tetrazolium as compared to pretreatment neutrophils. The administration of both recombinant forms of GCSF produced large increases in the bone marrow myeloid: erythroid (M:E) ratio concomitantly with the neutrophilias. This is the first preliminary report documenting the bone marrow response of cattle to the native and recombinant (rb-GCSF ser17) forms of bovine GCSF.
Crescentic Cataracts in Alderley Park Rats
Authors: Lazenby C. M. , Westwood F. R. , Greaves P.
Published: March 2010

The ophthalmoscopic appearances and the clinical evolution of a previously poorly documented form of crescentic cataract was studied in over 2,000 untreated Alderley Park rats between 4 and 110 weeks of age. In addition, 401 ex-breeder females, 54 gonadectomized males, and 56 gonadectomized females of the same strain were studied. The light microscopic features of the lenticular changes were also examined in detail. The cataracts, crescentic in shape and originating dorsally at the lens equator, were mostly unilateral. They appeared from about 30 weeks of age and affected 4% of intact males and 14% of intact females by about 2 years of age. Fewer cataracts were found in ex-breeder females, and none were found in male or female gonadectomized rats up to 2 years of age. The cataracts developed rapidly and became fully formed in 3 months. Subsequently, most cataracts scarcely progressed. Only a few extended to involve the entire lens. Some appeared to regress completely. Histologically, affected lens fibers showed swelling, globular disintegration, and liquefaction, most marked in the cortex medial to the lens bow area and extending along the direction of the lens fibers in an anterior and posterior direction but only occasionally reaching the lens capsule. The cause of these age-related lenticular changes in the Alderley Park rat is uncertain, but these changes are important during the conduct of long-term studies with this strain because their incidence can be modulated by agents that alter sex hormone status.
Immunohistochemical Evaluation of Canine Carcinomas with Monoclonal Antibody B72.3
Authors: Clemo F. A. S. , DeNicola D. B. , Delaney L. J.
Published: March 2010

Monoclonal antibody (MAb) B72.3 reacts with a tumor-associated glycoprotein, designated TAG-72. TAG-72 has been identified in many human carcinomas but generally is not found in normal human tissues. Because of its proven utility in the diagnosis of human carcinomas, MAb B72.3 was applied to several different types of canine carcinomas. Five types of formalin-fixed, paraffin-embedded canine carcinomas were evaluated for immunoreactivity with MAb B72.3 by use of an avidin biotin immunoperoxidase complex method. Samples were considered positive when ≥5% of all malignant cells contained a distinct intracellular stain. Immunoreactivity for MAb B72.3 was observed in 6/9 (67%) pulmonary adenocarcinomas, 7/13 (54%) transitional cell carcinomas, 7/11 (64%) mammary adenocarcinomas, 7/11 (64%) nasal adenocarcinomas, and 1/2 (50%) prostatic adenocarcinomas. The average cellular staining for positive carcinomas was 25%. Normal canine tissues from similar anatomic sites had little or no individual cell immunoreactivity. These preliminary results indicate that some canine carcinomas may express a tumor-associated antigen that is similar to TAG-72 and that MAb B72.3 immunoreactivity may be of diagnostic significance in classifying animal tumors.
Subepidermal Vesiculobullous Filarial Dermatitis in Free-ranging American Badgers(Taxidea taxus)
Authors: O'Toole D. , Williams E. S. , Welch V. , Nunamaker C. E. , lynn C.
Published: March 2010

Skin and superficial lymph nodes from the 65 juvenile (< 1 year old) and adult free-ranging American badgers (Taxidea taxus) of both sexes that were killed from late July to late October 1991 as part of the recovery program for the endangered black-footed ferret (Mustela nigripes) were examined for evidence of Filaria taxideae. Fifty-one badgers (51/64, 80%) were infected. Both adult badgers (30/32, 94%) and juvenile badgers (21/32, 67%) were infected by adult filarial worms, which occurred most commonly in subcutaneous tissues of the inguinal area, proximal thigh, and ventral abdomen. Sections of formalin-fixed skin and, from many badgers, subcutaneous lymph nodes were stained with hematoxylin and eosin, Jones' methenamine silver (for basement membrane), and an avidin biotin peroxidase complex method (for factor VIII-related antigen). Superficial dermatitis attributable to embryonated filarial ova and larvae was present in 26/64 badgers (41 %), all of them adult (> 1 year old). Acute lesions consisted of multifocal vesiculobullous dermoepidermal separation and superficial perivascular dermatitis. Ultrastructural examination and Jones' silver-stained sections revealed separation between basal keratinocytes and the basal lamina (subepidermal vesiculation). Older lesions consisted of ulcerative superficial granulomatous dermatitis associated with ova and larvae. Multifocal granulomatous endolymphangitis, which involved afferent lymphatics of subcutaneous lymph nodes, was associated with viable as well as degenerative ova and larvae. Adult filarial worms were found in the subcutis alone and did not provoke an inflammatory reaction.
Clinical Signs and Lesions in Gnotobiotic Pigs Inoculated with Shiga-like Toxin I fromEscherichia coli
Authors: Dykstra S. A. , Moxley R. A. , Janke B. H. , Nelson E. A. , Francis D. H.
Published: March 2010

Gnotobiotic pigs were used as a model to study the contribution of Shiga-like toxin I to natural disease caused by enterohemorrhagic Escherichia coli in calves and human beings. Eleven 2– to 7–day-old gnotobiotic pigs of either sex, obtained by closed hysterotomy, were injected intramuscularly with graded doses of partially purified Shiga-like toxin I derived from a lysogenized Escherichia coli strain. Four other gnotobiotic pigs were injected with a mock toxin preparation obtained from a nonlysogenized culture of the same E. coli strain. All toxin-injected pigs developed diarrhea, and three displayed signs of neurologic disease. Pigs either died or were euthanatized 2 to 4 days post-inoculation. Necrosis of muscle was grossly evident at the site of injection in all toxin-inoculated pigs. Hemorrhage in the lumen of the small and large intestines and blood in the feces were also evident in two toxin-inoculated pigs. Microscopically, severe necrotizing myositis at the injection site, multifocal encephalomalacia, and mucosal infarcts and hemorrhage in the small and large intestines were seen. In small vessels at lesion sites, endothelial cells were frequently swollen or necrotic. Pigs inoculated with mock toxin did not develop diarrhea or exhibit signs of neurologic disease, and the only apparent lesion was mild microscopic myositis at the injection site in 1/4 pigs. The results of this study indicate that Shiga-like toxin I causes vascular damage and ischemic necrosis in the intestines and brains of gnotobiotic pigs. These lesions are similar to those seen in the intestines of calves and human beings with hemorrhagic colitis and in the brains of human beings with thrombotic thrombocytopenic purpura.
Viral Antigen Distribution in Organs of Cattle Experimentally Infected with Rinderpest Virus
Authors: Wohlsein P. , Trautwein G. , Harder T. C. , Liess B. , Barrett T.
Published: March 2010

The distribution of viral antigen in various organs of four approximately 10-month-old castrated male Friesian cattle experimentally infected with a highly virulent strain of rinderpest virus was studied. A monoclonal antibody with genus-specific reactivity for morbilliviruses was applied in an indirect immunoperoxidase method performed on formalin-fixed, paraffin-embedded tissue sections. Rinderpest viral antigen was located mainly in the cytoplasm of the epithelial cells of the digestive, respiratory, and urinary tracts, as well as in the cells of endocrine glands (adrenal, thyroid) and exocrine glands (salivary glands, sebaceous glands, exocrine pancreas). Furthermore, different types of cells in lymphatic organs contained rinderpest viral antigen. In contrast to the documented results of studies carried out with other morbilliviruses, tissues of the central nervous system did not contain viral antigen. Various types of epithelial and lymphoreticular cells are the main targets of a virulent strain of rinderpest virus in vivo.
Comparison of the Antigen Distribution of Two US Porcine Reproductive and Respiratory Syndrome Virus Isolates with that of the Lelystad Virus
Authors: Halbur P. G. , Paul P. S. , Frey M. L. , Landgraf J. , Eernisse K. , Meng X.-J. , Andrews J. J. , Lum M. A. , Rathje J. A.
Published: March 2010

One hundred 4-week-old cesarean-derived colostrum-deprived pigs were inoculated with one of two different US porcine reproductive and respiratory syndrome virus (PRRSV) isolates (VR2385, VR2431) or the European Lelystad virus to detect and compare the location and amount of virus antigen. Interstitial pneumonia, myocarditis, lymphadenopathy, and encephalitis were consistently seen in all three groups; however, disease and lesions were more severe in the VR2385 group. Immunohistochemical evaluation of formalin-fixed tissues revealed virus antigen in alveolar macrophages in lungs of 22/25, 14/25, 14/25, and 0/25 of the VR2385, VR2431, Lelystad, and control pigs, respectively. Follicular macrophages and dendritic cells in the lymph nodes of 14/25, 10/25, 10/25, and 0/25 pigs from the VR2385, VR2431, Lelystad, and control groups, respectively, stained positive for virus antigen. Similar cells in the tonsils from 25/25, 21/25, 23/25, and 0/25 pigs from the VR2385, VR2431, Lelystad, and control groups, respectively, stained positive for virus antigen. Other tissues and cells in which virus antigen was detected included macrophages and endothelial cells in the heart, macrophages, and interdigitating cells in the thymus, macrophages and dendritic cells in the spleen and Peyer's patches, and macrophages in hepatic sinusoids, renal medullary interstitium, and adrenal gland. PRRSV persisted in macrophages in the lung, tonsil, lymph node, and spleen for at least 28 days. Significantly more PRRSV antigen was detected in the lung ( P < 0.01), lymph nodes ( P ≤ 0.05), and tonsils ( P < 0.05) of the VR2385 pigs than was detected in the same tissues of the VR2431 and Lelystad pigs. The cell types in which PRRSV antigen was detected and the distribution of PRRSV antigen-positive cells within particular tissues and organs were generally similar for the different virus inoculation groups despite differences in virulence of the isolates.
A Reverse Transcription-Quantitative Competitive Polymerase Chain Reaction (RT-qcPCR) Technique to Measure Cytokine Gene Expression in Domestic Mammals
Authors: Rottman J. B. , Tompkins W. A. F. , Tompkins M. B.
Published: March 2010

Inbred strains of rats and mice have long been used to study basic mechanisms of human disease. Our knowledge of the rodent and human immune systems has increased in recent years, largely because of the availability of reagents and techniques specific for these species. In contrast, outbred animals, including domestic companion and food animals, have not been used routinely as experimental models for human disease, largely because reagents and assays necessary for basic research in immunology and physiology have not been available. Here, using consensus cytokine nucleic acid sequences, we adapt a previously described reverse transcription-quantitative competitive polymerase chain reaction technique to measure interleukin 2 (IL2), IL4, IL6, IL10, IL12, interferon γ, tumor necrosis factor α, and glyceraldehyde-3-phosphate dehydrogenase mRNA expression in the cow, cat, dog, horse, and pig. We demonstrate that the assay is sensitive, accurate, and reproducible.
Primary Epitheliotropic Alimentary T-cell Lymphoma with Hepatic Involvement in a Dog
Authors: French R. A. , Seitz S. E. , Valli V. E. O.
Published: March 2010

The anatomic forms of lymphoma are multicentric, alimentary, thymic, cutaneous, and leukemic. Correlations between cell type and topographic distribution of lymphomas is not well documented, but there are more plasmacytoid tumors in the gut, skin, and spleen, which suggests that these are areas of malignant transformation preceded by a period of benign immune hyperplasia. Alimentary forms of lymphoma can be preceded by lymphocytic-plasmacytic enteritis. In the present case, an epitheliotropic alimentary form of T-cell lymphoma with hepatic involvement and concomitant lymphocytic-plasmacytic enteritis was diagnosed in an 8-year-old male Labrador Retriever. The lymphoma was characterized by the accumulation of atypical lymphocytes in the lamina propria and mucosal epithelium of the jejunum. The lymphocytes were identified as T-cell lineage using a polyclonal rabbit antisera to the human pan-T-cell determinant CD-3. The “homing” nature of the neoplasm resembles the epidermotropic form of cutaneous T-cell lymphoma.
Ubiquitin Expression in Degenerating Axons of Equine Cervical Compressive Myelopathy
Authors: Jortner B. S. , Scarratt W. K. , Modransky P. D. , Walton A. , Perkins S. K.
Published: March 2010

Neuropathologic examination revealed axonal swelling and breakdown leading to Wallerian degeneration of affected myelinated nerve fibers in the spinal cord white matter of four young horses with equine cervical compressive myelopathy. Immunohistochemical reactions for the cell stress protein ubiquitin revealed an enhanced presence in the swollen axons, which may reflect a role for ubiquitin in the neuronal catabolic process of axonal compression and degeneration in this myelopathy.
Intestinal Spirochetosis and Giardiasis in a Beagle Pup with Diarrhea
Authors: Duhamel G. E. , Hunsaker B. D. , Mathiesen M. R. , Moxley R. A.
Published: March 2010

This report describes the light microscopic and ultrastructural changes in a 3-month-old dog with naturally acquired intestinal spirochetosis and giardiasis. It was concluded that the pathogenetic characteristics of weakly β-hemolytic spirochetes associated with colitis in this pup were similar to those associated with human and porcine spirochetal diarrhea.
Intestinal Chlamydia in Finishing Pigs
Authors: Szeredi L. , Schiller I. , Sydler T. , Guscetti F. , Heinen E. , Corboz L. , Eggenberger E. , Jones G. E. , Pospischil A.
Published: March 2010

Gut and blood samples from 119 finishing pigs derived from 11 farms were collected during routine slaughter at an abattoir. Sections of formalin-fixed, paraffin-embedded tissues were labeled immunohistochemically using genus-specific, mouse monoclonal antibody against chlamydial lipopolysaccharide; goat polyclonal antiserum against the major outer membrane protein of Chlamydia trachomatis; and mouse monoclonal antibody against the ovine abortion subtype of C. psittaci. Gut samples from 33 of 111 (29.7%) individual pigs stained positive with the genus-specific monoclonal antibody, and of these 30 of 32 (93.7%) also reacted with the C. trachomatis-specific antiserum. Labeled inclusions were restricted to mature enterocytes of the large intestine in 33 of 111 cases. Infection of small intestinal enterocytes was noted in only one of 82 ileal samples. The blood samples were tested for antichlamydial antibodies by enzyme-linked immunosorbent assay (ELISA) and complement fixation test (CFT). With ELISA, 95 of the 115 sera tested (82.6%) yielded positive antichlamydial reactions. With CFT, 34 of the 119 sera tested (28.6%) were unequivocally positive (≥ 1: 10, 100% binding), and 10 (7.6%) yielded doubtful positive reactions (1: 10, 50-75% binding). Positive ELISA and CFT titers showed poor agreement ( K = 0.112), whereas the agreement between positive findings by immunohistochemical labeling and CFT was fair ( K = 0.205).
Sites of Replication of Bovine Respiratory Syncytial Virus in Naturally Infected Calves as Determined by In Situ Hybridization
Authors: Viuff B. , Uttenthal Å. , Tegtmeier C. , Alexandersen S.
Published: March 2010

Replication of bovine respiratory syncytial virus (BRSV) was studied in three naturally infected calves by in situ hybridization using strand-specific RNA probes. One of the calves was a 5-month-old Friesian, the other two calves were a 3-month-old and a 3-week-old Jersey. Two Jersey calves, 3 months and 3 weeks of age, served as controls. Replication of BRSV took place in the luminal lining of the respiratory tract. In one of the BRSV infected animals (calf No. 1), replication was especially seen in the bronchi, whereas in the two other animals (calf Nos. 2 and 3) replication of BRSV was demonstrated in the bronchiolar epithelial cells and in alveolar cells. Syncytia were often observed in the bronchiolar walls and in alveoli and such syncytia were always replicating BRSV. By immunohistochemistry it was possible to demonstrate BRSV antigen at the same location as replication of BRSV was detected. In tissue outside the respiratory tract neither BRSV antigen nor replication of BRSV could be demonstrated.
Adenocarcinoma of the Hepatopancreatic Ampulla in a Domestic Cat
Authors: Haines V. L. , Brown P. R. , Hruban R. H. , Huso D. L.
Published: March 2010

A 13-year-old spayed female Siamese cat was submitted for necropsy following unsuccessful treatment for obstructive jaundice. Histopathologic examination revealed an adenocarcinoma of the hepatopancreatic ampulla. The carcinoma obstructed the pancreatic and common bile ducts entering the ampulla, resulting in severe diffuse acinar degeneration, atrophy and fibrosis of the pancreas, and dilatation of the bile ducts, biliary fibrosis, and ductule proliferation in the liver. In humans, carcinoma of the ampulla of Vater, the hepatopancreatic ampulla, is considered an uncommon malignancy.
High Incidence and Histogenesis of Seminal Vesicle Adenocarcinoma and Lower Incidence of Prostate Carcinomas in the Lobund-Wistar Prostate Cancer Rat Model Using N-nitrosomethylurea and Testosterone
Authors: Tamano S. , Rehm S. , Waalkes M. P. , Ward J. M.
Published: March 2010

The origin of chemically induced male accessory sex gland tumors was studied in Lobund-Wistar rats. Rats were treated at the age of 3 months with a single intravenous injection of 30 mg N-nitrosomethylurea (NMU)/kg body weight and given subcutaneous silastic implants filled with 40 mg testosterone propionate. Previous reports described a high incidence of prostate carcinomas in these rats with this treatment protocol. Additional animal groups included untreated controls, rats that received only an injection of 30 mg NMU/kg, and rats that were subjected to ablation of the seminal vesicle lobes prior to the treatment with NMU and testosterone. Three to 14 rats per group were sacrificed 4 to 10 months after NMU treatment and all remaining rats after 12 months. Twenty-four additional rats died or became moribund during the study. All rats were necropsied and the dorsolateral and ventral prostate and seminal vesicles with coagulating gland (anterior prostate) were examined histologically according to a standardized protocol. Lesions detected included atypical hyperplasia in all glands (resembling prostate intraepithelial neoplasia of human beings), adenomas in seminal vesicles only, and early carcinomas and adenocarcinomas in seminal vesicles and coagulating gland. Early carcinomas of the seminal vesicle, microscopically small and with invasion of the lamina propria and/or tunica muscularis, were detected as rapidly as 4 months after treatment. The vast majority (>95%) of the grossly visible nodules/masses originated from the seminal vesicles. Testosterone treatment enhanced occurrence and increased the incidence of all lesions, particularly of seminal vesicle adenocarcinomas, from 30% (7/23) to 64% (21/33). Coagulating gland tumors were found in 21% (7/33) of the rats. Ablation of the seminal vesicle lobes reduced the incidence of seminal vesicle adenocarcinomas to 11% (3/29), and these tumors arose from tissues remaining within the parenchyma of the seminal vesicle/prostate complex after ablation. Thus, NMU-induced and testosterone-promoted male sex gland tumors of the Lobund-Wistar rat arise almost exclusively in the seminal vesicles and coagulating gland (anterior prostate), are highly invasive in seminal vesicles before attaining a grossly visible size, and progress rapidly within 4 months, spreading to adjacent tissues and other organs.
Effect of Sn addition on porosity and microstructure of products of self-propagating high temperature synthesis reaction of Al–Ti–C system
Authors: Li Y. X. , Hu J. D. , Wang H. Y. , Guo Z. X
Published: March 2010

Effect of Sn addition on the self-propagating high temperature synthesis reaction has been investigated. The results show that Sn serves not only as a diluent but also as a reactant and reacts with Ti to form Ti6Sn5 phase. As the Sn content ranges from 6 to 15 wt-%, the combustion temperature of the system decreases and the porosity of the products is reduced, however, the size of TiC particulate decreases and the shape of TiC particulate has significantly changed in the SHS reaction products. Specially, when Sn content is over 12 wt-%, the shape of TiC particles gradually transforms from the multi-angular shape to the spherical shape. The in situ formed master alloy containing Al and Sn, as well as a large volume fraction of TiC particulates is successfully synthesised.
Pim2 cooperates with PML-RARα to induce acute myeloid leukemia in a bone marrow transplantation model
Authors: Agrawal-Singh Shuchi , Koschmieder Steffen , Gelsing Sandra , Stocking Carol , Stehling Martin , Thiede Christian , Thoennissen Nils H. , Köhler Gabriele , Valk Peter J. M. , Delwel Ruud , Mills Ken , Bäumer Nicole , Tickenbrock Lara , Hansen Klaus , Berdel Wolfgang E. , Müller-Tidow Carsten , Serve Hubert
Published: March 2010

Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative role of Pim2 with promyelocytic leukemia/retinoic acid receptor α (PML/RARα), we used a well-established PML-RARα (PRα) mouse model. Pim2 coexpression in PRα-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PRα cells were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PRα alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PRα cells contained a slightly higher fraction of immature myeloid cells, compared with the previously described APL disease induced by PRα. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon all-trans retinoic acid (ATRA) treatment in vitro. These results support the hypothesis that Pim2, which is also a known target of Flt3-ITD (another gene that cooperates with PML-RARα), cooperates with PRα to induce APL-like disease.
Multimodal investigations of trans-endothelial cell trafficking under condition of disrupted blood-brain barrier integrity
Authors: Marchi Nicola , Teng Qingshan , Nguyen Minh T , Franic Linda , Desai Nirav K , Masaryk Thomas , Rasmussen Peter , Trasciatti Silvia , Janigro Damir
Published: March 2010

Background

Stem cells or immune cells targeting the central nervous system (CNS) bear significant promises for patients affected by CNS disorders. Brain or spinal cord delivery of therapeutic cells is limited by the blood-brain barrier (BBB) which remains one of the recognized rate-limiting steps. Osmotic BBB disruption (BBBD) has been shown to improve small molecule chemotherapy for brain tumors, but successful delivery of cells in conjunction with BBBD has never been reported.

We have used a clinically relevant model (pig) of BBBD to attempt brain delivery of TALL-104, a human leukemic T cell line. TALL-104 cells are potent tumor killers and have demonstrated potential for systemic tumor therapy. The pig model used is analogous to the clinical BBBD procedure. Cells were injected in the carotid artery after labeling with the MRI T1 contrast agent GdHPDO3A. Contrast CT scans were used to quantify BBBD and MRI was used to detect Gd++-loaded cells in the brain. Transcranial Doppler was used to monitor cerebral blood flow. EEG recordings were used to detect seizures. Immunocytochemical detection (Cresyl Violet, anti-human CD8 for TALL-104, Evans Blue for BBB damage, GFAP and NEUN) was performed.

Results

At the concentration used TALL-104 cells were tolerated. Incomplete BBBD did not allow cell entry into the brain. MRI scans at 24 and 48 hours post-injection allowed visualization of topographically segregated cells in the hemisphere that underwent successful BBBD. Perivascular location of TALL-104 was confirmed in the BBBD hemisphere by Cresyl violet and CD8 immunocytochemistry. No significant alteration in CBF or EEG activity was recorded during cell injections.

Conclusions

Our data show that targeted CNS cell therapy requires blood-brain barrier disruption. MRI-detectable cytotoxic anti-neoplastic cells can be forced to transverse the BBB and accumulate in the perivascular space. The virtual absence of toxicity, the high anti-tumor activity of TALL-104, and the clinical feasibility of human osmotic BBBD suggest that this approach may be adopted to treat brain or spinal cord tumors. In addition, BBBD may favor CNS entry of other cells that normally lack CNS tropism.
Small chloroplast-targeted DnaJ proteins are involved in optimization of photosynthetic reactions in Arabidopsis thaliana
Authors: Chen Kun-Ming , Holmström Maija , Raksajit Wuttinun , Suorsa Marjaana , Piippo Mirva , Aro Eva-Mari
Published: March 2010

Background

DnaJ proteins participate in many metabolic pathways through dynamic interactions with various components of these processes. The role of three small chloroplast-targeted DnaJ proteins, AtJ8 (At1 g80920), AtJ11 (At4 g36040) and AtJ20 (At4 g13830), was investigated here using knock-out mutants of Arabidopsis thaliana. Photochemical efficiency, capacity of CO2 assimilation, stabilization of Photosystem (PS) II dimers and supercomplexes under high light illumination, energy distribution between PSI and PSII and phosphorylation of PSII-LHCII proteins, global gene expression profiles and oxidative stress responses of these DnaJ mutants were analyzed.

Results

Knockout of one of these proteins caused a series of events including a decrease in photosynthetic efficiency, destabilization of PSII complexes and loss of control for balancing the redox reactions in chloroplasts. Data obtained with DNA microarray analysis demonstrated that the lack of one of these DnaJ proteins triggers a global stress response and therefore confers the plants greater tolerance to oxidative stress induced by high light or methyl viologen treatments. Expression of a set of genes encoding enzymes that detoxify reactive oxygen species (ROS) as well as a number of stress-related transcription factors behaved in the mutants at growth light similarly to that when wild-type (WT) plants were transferred to high light. Also a set of genes related to redox regulation were upregulated in the mutants. On the other hand, although the three DnaJ proteins reside in chloroplasts, the expression of most genes encoding thylakoid membrane proteins was not changed in the mutants.

Conclusion

It is proposed that the tolerance of the DnaJ protein knockout plants to oxidative stress occurs at the expense of the flexibility of photosynthetic reactions. Despite the fact that the effects of the individual protein knockout on the response of plants to high light treatment are quite similar, it is conceivable that both specific- and cross-talk functions exist between the three small chloroplast-targeted DnaJ proteins, AtJ8, AtJ11 and AtJ20.
Small intestinal mucosa expression of putative chaperone fls485
Authors: Reinartz Andrea , Ehling Josef , Franz Susanne , Simon Verena , Bravo Ignacio G , Tessmer Claudia , Zentgraf Hanswalter , Lyer Stefan , Schneider Ursula , Köster Jan , Raupach Kerstin , Kämmerer Elke , Klaus Christina , Tischendorf Jens JW , Kopitz Jürgen , Alonso Angel , Gassler Nikolaus
Published: March 2010

Background

Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. fls485 coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze fls485 expression in human small intestinal mucosa.

Methods

fls485 expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several in situ techniques and usage of newly synthesized mouse monoclonal antibodies.

Results

fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.

Conclusions

Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.
Enhanced antiproliferative and apoptotic response to combined treatment of γ-tocotrienol with erlotinib or gefitinib in mammary tumor cells
Authors: Bachawal Sunitha V , Wali Vikram B , Sylvester Paul W
Published: March 2010

Background

Aberrant ErbB receptor signaling is associated with various types of malignancies. γ-Tocotrienol is a member of the vitamin E family of compounds that displays potent anticancer activity that is associated with suppression in ErbB receptor phosphorylation and mitogenic signaling. Erlotinib and gefitinib are tyrosine kinase inhibitors that block ErbB1 receptor activation, whereas trastuzumab is a monoclonal antibody that has been designed to specifically inhibit ErbB2 receptor activation. However, the clinical effectiveness of these agents have been disappointing because of cooperation between different ErbB family members that can rescue cancer cells from agents directed against a single ErbB receptor subtype. It was hypothesized that targeting multiple ErbB receptor subtypes with combined treatment of γ-tocotrienol and ErbB receptor inhibitors would provide greater anticancer effects than monotherapy targeting only a single ErbB receptor subtype.

Methods

Highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined media containing 10 ng/ml EGF as a mitogen. Cell viability wase determined by MTT assay, whereas Western blot and immunofluorescent staining was used to determine treatment effects on ErbB receptor subtype level and activation. Treatment-induced apoptosis was determined using annexin V staining and Western blot analysis of cleaved caspase-3 and PARP levels.

Results

Treatment with 3.5 μM γ-tocotrienol, 0.5 μM erlotinib or 1.0 μM gefitinib alone, significantly inhibited +SA tumor cell growth. Combined treatment with subeffective doses of erlotinib (0.25 μM) or gefitinib (0.5 μM) with subeffective doses of γ-tocotrienol (0.5-3.0 μM) significantly inhibited the growth and induced apoptosis in a dose-responsive manner. Trastuzumab treatment alone or in combination had no effect on +SA cell growth and viability. Combined treatment of γ-tocotrienol with erlotinib or gefitinib also cause a large decrease in ErbB3, ErbB4, and to a lesser extent ErbB2 receptor levels, and EGF-dependent ErbB2-4 tyrosine phosphorylation (activation), but had no effect on ErbB1 receptor levels or activation.

Conclusion

Combination treatment of γ-tocotrienol with specific ErbB receptor inhibitors is more effective in reducing mammary tumor cell growth and viability than high dose monotherapy, suggesting that targeting multiple ErbB receptors with combination therapy may significantly improve the therapeutic response in breast cancer patients.
CD40 ligand induced cytotoxicity in carcinoma cells is enhanced by inhibition of metalloproteinase cleavage and delivery via a conditionally-replicating adenovirus
Authors: Elmetwali Taha , Searle Peter F , McNeish Iain , Young Lawrence S , Palmer Daniel H
Published: March 2010

Background

CD40 and its ligand (CD40L) play a critical role in co-ordinating immune responses. CD40 is also expressed in lymphoid malignancies and a number of carcinomas. In carcinoma cells the physiological outcome of CD40 ligation depends on the level of receptor engagement with low levels promoting cell survival and high levels inducing cell death. The most profound induction of cell death in carcinoma cells is induced by membrane-bound rather than recombinant soluble CD40L, but like other TNF family ligands, it is cleaved from the membrane by matrix metalloproteinases.

Results

We have generated a replication-deficient adenovirus expressing a mutant CD40L that is resistant to metalloproteinase cleavage such that ligand expression is retained at the cell membrane. Here we show that the mutated, cleavage-resistant form of CD40L is a more potent inducer of apoptosis than wild-type ligand in CD40-positive carcinoma cell lines. Since transgene expression via replication-deficient adenovirus vectors in vivo is low, we have also engineered a conditionally replicating E1A-CR2 deleted adenovirus to express mutant CD40L, resulting in significant amplification of ligand expression and consequent enhancement of its therapeutic effect.

Conclusions

Combined with numerous studies demonstrating its immunotherapeutic potential, these data provide a strong rationale for the exploitation of the CD40-CD40L pathway for the treatment of solid tumours.
Role of Palliative Care in Adolescent and Young Adult Oncology
Authors: Wein Simon , Pery Shlomit , Zer Alona
Published: March 2010

Adolescents and young adults (AYAs) with cancer are a heterogeneous group. Nevertheless, there are sufficient unifying characteristics to form a distinct clinical entity. Management of this special group requires a broad-based interdisciplinary clinical team, which should include palliative care (PC), psychology, social work, oncology, and nursing representatives. The function of PC is to provide impeccable pain and other symptom control and to coordinate care as the disease progresses. Features unique to AYAs with cancer include the psychosocial developmental phases, a young person facing death, grief, and bereavement. Pharmacologic and medical interventions by PC in AYAs are broadly similar to adults. Developing trust and being flexible are key skills that PC must use with AYAs. There is a paucity of high-quality controlled studies in the PC literature in general and AYA-PC in particular. Therefore, the methodology of this article is largely based on the narrative and clinical experience. The experience is based on clinicians' work with AYAs with cancer in Israel and Australia. Clinical lessons will be drawn by comparing and contrasting the cultures. Nevertheless, most PC clinical interventions, both pharmacologic and psychosocial, are derived from literature where there is a good evidence base. Future development of PC within AYAs should be coordinated at a national level via appropriate palliative and oncology professional organizations.
An interview with Rong Li
Authors: Senior Kathryn
Published: March 2010

Rong Li is an Investigator at the Stowers Institute for Medical Research, Kansas City, USA. Her lab is made up of a lively team who are all fascinated by cellular asymmetry, division and evolution. Rong joined Development as an editor in 2009. We interviewed Rong to find out about her work and career, her interest in developmental biology and her new role with the journal.
CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function
Authors: Beqqali Abdelaziz , Monshouwer-Kloots Jantine , Monteiro Rui , Welling Maaike , Bakkers Jeroen , Ehler Elisabeth , Verkleij Arie , Mummery Christine , Passier Robert
Published: March 2010

In recent years, the perception of Z-disc function has changed from a passive anchor for myofilaments that allows transmission of force, to a dynamic multicomplex structure, capable of sensing and transducing extracellular signals. Here, we describe a new Z-disc protein, which we named CHAP (cytoskeletal heart-enriched actin-associated protein), expressed in differentiating heart and skeletal muscle in vitro and in vivo. Interestingly, in addition to its sarcomeric localization, CHAP was also able to translocate to the nucleus. CHAP was associated with filamentous actin in the cytoplasm and the nucleus when expressed ectopically in vitro, but in rat neonatal cardiomyocytes, CHAP disrupted the subcellular localization of α-actinin, another Z-disc protein. More importantly, knockdown of CHAP in zebrafish resulted in aberrant cardiac and skeletal muscle development and function. These findings suggest that CHAP is a critical component of the sarcomere with an important role in muscle development.
A Square-planar Ni(II) Complex with an Asymmetric N2S2 Donor Set as a Model for the Active Site of Nickel-containing SOD: Structural Conversion Driven by Addition of a Strong Donor Ligand in the High Oxidation State
Authors: Nakane Daisuke , Funahashi Yasuhiro , Ozawa Tomohiro , Masuda Hideki
Published: March 2010

A novel Ni(II) complex with an asymmetric monoamino–monoamidato–dithioether square-planar coordination (1) was prepared as a model compound of the active center of NiSOD and characterized by spectroscopic and electrochemical methods. EPR data indicate that the structure of complex 1 in the high oxidation state can be significantly altered upon binding of imidazole, a stronger donor ligand than the original supporting ligand.
Determination of Easy Magnetization Axis of Mordenite Zeolite
Authors: Matsunaga Chika , Uchikoshi Tetsuo , Suzuki Tohru S , Sakka Yoshio , Matsuda Motohide
Published: March 2010

The easy-magnetization axis of mordenite zeolite was determined using commercially available mordenite powder. The well-dispersed suspension of the powder was consolidated by slip casting in a 12-T static magnetic field. The thick bulk deposit was cut into a dice in order to investigate the XRD patterns from the mutually orthogonal surfaces of the consolidated mordenite compacts, the normal lines of which surfaces were parallel and perpendicular to the applied magnetic field. The easy-magnetization axis of mordenite was determined to be the b axis based on the XRD measurements.
Photocatalytic Homogeneous Oxidation of Organic Compounds in Aqueous Solutions Containing Iron(III) Ion: A Very Simple Method for Mineralization of Organic Pollutants in Water
Authors: Imanishi Masachiyo , Hashimoto Keiji , Kominami Hiroshi
Published: March 2010

Irradiation of UV light to aqueous solutions of various organic compounds (acetic acid, alcohols, ketones, phenol, and benzenesulfonic acid) containing a small amount of metal ions was examined under an aerated condition at room temperature. These organic compounds were quantitatively decomposed to carbon dioxide in the presence of iron(III) ion, indicating that hydrated iron(III) complex acted as an efficient homogeneous photocatalyst.
Photocatalytic Hydrogen Production from Water Using Heterogeneous Two-dimensional Rhodium Coordination Polymer [Rh2(p-BDC)2]n
Authors: Kataoka Yusuke , Sato Konomi , Miyazaki Yuhei , Suzuki Yuto , Tanaka Hiroshi , Kitagawa Yasutaka , Kawakami Takashi , Okumura Mitsutaka , Mori Wasuke
Published: March 2010

Heterogeneous dinuclear rhodium(II) coordination polymer, [Rh2(p-BDC)2]n (p-BDC = 1,4-benzenedicarboxylate), which formed self-assembly infinite two-dimentional slit sheets structure was performed as hydrogen production catalyst for photochemical reduction of water under visible light irradiation in the presence of a multicomponent system containing Ru(bpy)32+, MV2+, and EDTA–2Na.
CAN/I2-catalyzed Chemoselective Synthesis of Thiosulfonates by Oxidation of Disulfides or Thiols
Authors: Cai Ming-Tiao , Lv Guang-Shu , Chen Jiu-Xi , Gao Wen-Xia , Ding Jin-Chang , Wu Hua-Yue
Published: March 2010

CAN/I2 promoted synthesis of thiosulfonates by oxidation of disulfides and thiols with high chemoselectivity and excellent yields in wet poly(ethylene glycol) (PEG-400). The overall process is simple, practical, and it provides convenient access to thiosulfonates.