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An apex nodule was recently identified in the urinary bladder of Scottish Terriers being screened for bladder cancer at our institution. This prospective, single-center, case series study was performed to better characterize the apex nodule and assess the clinical importance of the nodule. Scottish Terriers ≥6 years of age with no evidence of urinary tract disease underwent urinary tract ultrasonography and urinalysis at 6-month intervals. In dogs with evidence of the apex nodule, ultrasound features such as location, margins, number, echogenicity, size, and shape of the lesion were recorded by a veterinary oncologist and veterinary radiologist. The apex nodule was identified in eight (6%) of 134 dogs in the absence of other detectable bladder disease. Features of the nodules included the following: one nodule per dog, triangular to an oval shape, smooth mucosal covering, well-defined margins, isoechoic to the bladder wall, 2-4 mm at the base, and 4-6 mm protruding into the bladder lumen. In five dogs undergoing multiple ultrasonographic examinations, the nodule did not appear to change over time (up to 3.5 years). Cystoscopy performed in three dogs revealed a column of tissue covered by normal mucosa protruding into the bladder lumen. Histological features consistent with a neoplastic growth were absent. Five dogs remained free of any bladder disease. Three dogs developed urothelial carcinoma at sites distant to the nodule at 8-53 months after the nodule was first observed. Findings indicated that incidental apex nodules could mimic neoplasia and other bladder diseases in Scottish Terriers.

Background The 15-F2 -isoprostanes are by-products of oxidative stress and are increased in the urine of people with lower urinary tract diseases (LUTD), especially urinary neoplasia. Urothelial carcinoma (UC) is the most common urinary neoplasm in dogs. Earlier detection of UC by noninvasive means could lead to improved outcomes. Urinary 15-F2 -isoprostanes potentially could provide this means, but have not been evaluated in dogs with UC. Objective The objective of this study was to measure urinary 15-F2 -isoprostanes in dogs with UC and dogs with other LUTD. Animals One hundred seventeen dogs: 46 dogs with UC, 30 dogs with LUTD, and 25 control dogs. Methods Any dog that was presented with dysuria was eligible for inclusion. Diagnosis of UC was confirmed histologically. Urinalysis was performed in each case, and 15-F2 -isoprostanes quantified by gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS) and normalized to urinary creatinine concentration. Results Dogs with urinary diseases (UC + LUTD) had higher median urinary 15-F2 -isoprostanes when compared to control dogs (5.92 ng/mg [range, 0.46-31.03] vs 3.73 [range, 1.8-7.98]; P = .02). Urinary 15-F2 -isoprostanes were similar in dogs with UC (5.33 ng/mg [range, 0.46-31.03]) compared to dogs with LUTD (6.29 ng/mg [range, 0.54-18.93]; P = .47) and control dogs (P = .06). Dogs with UC had higher qualitative measures of proteinuria (P = .004), hematuria (P = .01), and epithelial cells on urinalysis (P = .002) compared to the other groups. Conclusions and clinical importance Urinary F2 -isoprostanes are not useful for the detection of UC in dogs. Future research could evaluate urinary 15-F2 -isoprostanes as a marker of inflammation in disease progression and prognosis.

Objective To develop and establish the reliability, validity, measurement error, and minimum detectable change of a novel 30‐second fast‐paced walk test (30SFW) in persons with knee osteoarthritis (OA) that is easy to administer and can quantify walking performance in persons of all abilities. Methods Twenty females with symptomatic knee OA (mean age [SD] 58.30 [8.05] years) and 20 age‐ and sex‐matched asymptomatic controls (57.25 [8.71] years) participated in the study. Participants completed questionnaires of demographic and clinical data, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 36‐item Short Form Health Survey (SF‐36) followed by 30SFW performance. Participants returned 2‐7 days later and performed the 30SFW again. Results The knee OA group reported function that was worse than controls (all KOOS subscales; P < 0.0001). The 30SFW intrarater and interrater reliability were excellent [ICC (2,1) = 0.95‐0.99]. Knee OA participants walked a shorter distance in the 30SFW than controls (mean [SD]: OA 44.4 m [9.5 m]; control 58.1 m [7.8 m]; P < 0.0001). Positive strong correlations were found between the 30SFW and the KOOS–Activity of Daily Living, SF‐36‐Physical Functioning, and SF‐36‐Physical Health Composite scores (P < 0.0001). A nonsignificant, weak correlation between 30SFW and SF‐36‐Mental Health scores was present (r = 0.32, P = 0.05). Conclusion The 30SFW has excellent intrarater and interrater reliability. The 30SFW demonstrated excellent known groups, convergent, and discriminant validity as a measure of short‐distance walking ability in persons with knee OA. Clinicians and researchers should consider using the 30SFW to quantify walking ability in persons with knee OA and assess walking ability change.

The purpose of this study was to determine the plasma pharmacokinetics (PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC-MS/MS following an oral zebularine dose of 8 or 4 mg kg-1 . Plasma zebularine clearance was constant. Mean maximum concentration (Cmax ) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg-1 , respectively. Mean half-life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg-1 , respectively. A single 8 mg kg-1 dose was well tolerated. Daily 4 mg kg-1 treatment in three laboratory dogs resulted in grade 4 neutropenia (n = 3), grade 1 anorexia (n = 2) and grade 1 or 2 dermatologic changes (n = 2). All adverse events resolved with supportive care. A 4 mg kg-1 dose every 21 days was well tolerated. A follow-up dose escalation study is in progress with a lower starting dose.

Background Transitional cell carcinoma (TCC) of the urinary bladder of dogs can be a difficult cancer to treat, and effective therapies are limited. Vinblastine has been used in humans with TCC and has potent anti-proliferative effects against canine TCC cells in vitro. Objectives To determine the antitumor activity and toxicoses of vinblastine in dogs with urinary bladder TCC. Animals Animals selected were 28 privately owned dogs that presented to the Purdue University Veterinary Teaching Hospital (PUVTH) with measurable, histologically confirmed TCC. Methods Prospective clinical trial: The starting vinblastine dosage was 3.0 mg/m2IV every 2 weeks. Treatment continued until cancer progression or unacceptable toxicoses occurred. Complete evaluations (physical exam, complete blood count [CBC], serum biochemical profile, urinalysis, thoracic radiography, abdominal ultrasound [US]) were performed at 8-week intervals. Urinary tract US with bladder tumor mapping was performed monthly. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria. Results Tumor responses included 10 (36%) partial remission, 14 (50%) stable disease, and 4 (14%) progressive disease. The median progression free interval was 122 days (range, 28–399 days). The median survival time was 147 days (range, 28–476 days) from 1st vinblastine treatment to death and 299 days (range, 43–921 days) from diagnosis to death. The majority of dogs (27 of 28) did not have clinically relevant adverse effects. Seventeen of 28 (61%) dogs required dosage reductions because of neutropenia. Conclusion and Clinical Importance Vinblastine has antitumor activity against TCC in dogs and can be considered another treatment option for this cancer.

The purpose of this study was to assess the toxicoses and antitumor activity of metronomic chlorambucil at a dosage of 4 mg m(-2) daily in dogs with naturally occurring cancer. Thirty-six dogs were enrolled in the study. The protocol was well tolerated with no grade 3 or 4 toxicoses noted. Complete remission was achieved, and lasted over 35 weeks in three dogs (mast cell tumour, soft tissue sarcoma and thyroid carcinoma). Partial remission was noted in 1 dog with histiocytic sarcoma (39 weeks duration) for an overall remission rate of 11% (4 of 36). Stable disease was noted in 17 dogs (47%) with various other cancers. The median progression-free interval was 61 days, and the median survival time was 153 days. Chlorambucil given in a metronomic protocol showed antitumor activity in dogs with a variety of naturally occurring cancers.

Inhibition of cyclooxygenase-2 (COX-2) represents a possible avenue for the prevention and/or treatment of some cancers. Our goal was to compare the effect of a selective inhibitor of COX-2, deracoxib, and a COX-1 and -2 inhibitor, piroxicam, on the growth of canine mammary tumours in a murine model. CMT-9 was used to induce xenografts in nude mice. Mice were treated with piroxicam (0.6 mg kg(-1)), deracoxib (6 mg kg(-1)) or a control solution. Tumour volumes between 0 and 24 days post-treatment showed no significant difference between all groups. A second series of experiments was performed with a higher dose of piroxicam (0.9 mg kg(-1)). Tumour volumes between 14 and 21 days post-treatment were significantly smaller in piroxicam-treated mice compared with controls. These results demonstrate that COX inhibition reduced the growth of canine mammary cancer xenografts in mice, suggesting that COX inhibitors could have a positive effect in dogs.

Background: Transitional cell carcinoma (TCC) is the most common cancer of the urinary tract in dogs. The most frequent cause of death is urinary obstruction from the primary tumor. Standard medical therapy for TCC is only partially effective. Hypothesis/Objectives: Intravesical administration of mitomycin C (MMC) in dogs with invasive TCC will result in antitumor activity against the primary tumor and minimal systemic drug absorption. Animals: Thirteen privately owned dogs with naturally occurring, histopathologically diagnosed TCC of the urinary bladder. Methods: A prospective phase I trial was performed. MMC was given intravesically (600 μg/mL initial concentration) for 1 h/d for 2 consecutive days each month. The MMC concentration was escalated to a maximum of 800 μg/mL in groups of 3 dogs until the maximum tolerated dose (MTD) was determined. Serum assays for MMC were performed to determine the extent of systemic absorption of the MMC. Results: The MTD of MMC based on local toxicoses was 700 μg/mL (1-h dwell time, 2 consecutive days). In addition, 2 dogs had severe myelosuppression and appeared to have systemic absorption of MMC. Five dogs had partial remission, and 7 dogs had stable disease. Conclusions: Intravesical MMC has antitumor activity in dogs with invasive TCC. Further study is needed to determine the cause of the myelosuppression associated with MMC administration, and to develop strategies to minimize this risk.

Zusammenfassung Aus 1206 Kotproben, die von klinisch gesunden Schlachtschweinen, wahrend eines Zeitraumes von 14 Monaten (November 1979 bis Dezember 1980) entnommen worden waren, gelang die Isolierung von 33 Y. enterocolitica- und 7 Y. pseudotuberculosis-Stammen. 32 bzw. 1 der Y. enterocolitica-Stamme gehorten der O-Gruppe I bzw. V an, wahrend 1, 4 bzw. 2 der Stamme von Y. pseudotuberculosis auf die Serotypen I, II bzw. III entfielen. Bei 2 Tieren lag eine Mischkultur mit beiden Erregerarten vor. Y. enterocolitica wurde in den Spatherbst-, Winter- und Fruhjahrsmonaten, mit der hochsten Inzidenz im Januar (13,7%) nachgewiesen, wahrend Y. pseudotuberculosis nur in den Wintermonaten, mit der grosten Nachweisquote im Januar (3,2%), isoliert werden konnte. Die bakteriologischen Befunde und ihre Bedeutung fur den Menschen werden diskutiert. Frau C. Lembke danken wir fur die wertvolle technische Assistenz. Summary Isolation of Yersinia enterocolitica and Yersinia pseudotuberculosis from faeces samples of healthy slaughter pigs in relation to season of year 33 strains of Y. enterocolitica and 7 strains of Y. pseudotuberculosis were isolated from 1206 faeces samples collected during 14 months (November 1979 to December 1980) from clinically healthy slaughter pigs. 32 strains and 1 strain, respectively, of Y. enterocolitica belonged to O-groups I and V; 1, 4 and 2 strains, respectively, of Y. pseudotuberculosis were of serotypes I, II and III respectively. In 2 faeces samples both species were identified. Y. enterocolitica was isolated during the months of late autumn, winter and spring, with the highest incidence (13.7%) in January. Y. pseudotuberculosis was only found in the winter months, with the highest recovery rate (3.2%) in January. The bacteriological findings and their relevance for man are discussed. Resume Mise en evidence de Yersinia enterocolitica et de Yersinia pseudotuberculosis dans des matieres fecales de porcs en bonne sante aux abattoirs en fonction de la saison 33 souches de Y. enterocolitica et 7 souches de Y. pseudotuberculosis ont ete isolees a partir de 1206 echantillons de matieres fecales recoltes pendant 14 mois (novembre 1979 a decembre 1980) chez des porcs d'abattage cliniquement sains. 32 souches de Y. enterocolitica appartenaient au groupe OI et 1 souche au groupe OV; 1, 4 et 2 souches de Y. pseudotuberculosis appartenaient respectivement au serotype I, II et III. Une culture mixte des deux germes a ete trouvee chez 2 animaux. Y. enterocolitica a pu etre isolee pendant les mois de l'arriere-automne, d'hiver et du debut du printemps avec le taux le plus eleve en janvier (13,7%). Y. pseudotuberculosis n'a pu etre isolee que dans les mois d'hiver, avec le taux le plus eleve en janvier (3,2%). Les resultats bacteriologiques et leur signification pour l'etre humain sont discutes. Resumen Identificacion de Yersinia enterocolitica y Yersinia pseudotuberculosis en muestras de heces de cerdos sanos de abasto en dependencia de la estacion del ano De 1.206 muestras de heces, tomadas de cerdos de abasto, sanos clinicamente, durante un espacio de tiempo de 14 meses (Noviembre 1.979 hasta Diciembre 1.980), se logro el aislamiento de 33 estirpes Y. enterocolitica y 7 Y. pseudotuberculosis. 32 respectivamente 1 de las cepas de Y. enterocolitica pertenecian al grupo 0 I y V, resp., mientras que 1, 4 resp. 2 de las estirpes de Y. pseudotuberculosis correspondian a los serotipos I, II resp. III. En 2 animales se hallaron ambas especies bacterianas juntas. Y. enterocolitica se aislo durante los meses de otono tardio, invierno y primavera con una incidencia maxima en Enero (13,7%), mientras que Y. pseudotuberculosis en los meses de invierno nada mas, con una cuota maxima de recuperacion en Enero (3,2%). Se discuten los hallazgos bacteriologicos y su significancia para el hombre.

Differential expression of fucosylated glycoproteins has been correlated with malignancy and metastatic potential in various types of neoplasia. Utilizing glycoproteomics techniques, changes in fucosylated serum peptides associated with naturally occurring canine lymphoma and transitional cell carcinoma (TCC) have been evaluated. In both types of neoplasia, the majority of the fucosylated peptides that changed increased with the cancer. In one lymphoma case that was examined over the course of the disease, the same fucosylated peptides that increased during pre-chemotherapy decreased during post-chemotherapy, and then subsequently increased upon recurrence of the lymphoma. When comparing all the fucosylated peptides that increased in both types of cancer, there were only two peptides in common allowing discrimination between lymphoma and TCC based on their peptide profiles. These results emphasize the prospect of glycopeptide profiling in proteomics for use in discovering a panel of non-invasive, diagnostic or prognostic biomarkers of cancer.

Mineral weathering plays an important role in the global cycling of carbon and metals and there is an increasing realization that subsurface microbial activity may be a key factor controlling specific biogeochemical reactions and their rates. Methanobactin (mb) is an extracellular copper-binding compound excreted by methanotrophs to acquire copper for the regulation of methane oxidation. Bioavailable Cu regulates the expression and activity of pMMO vs. sMMO (particulate vs. soluble methane monooxygenase, respectively), key enzymes responsible for bacterial methane oxidation. In this study, we investigate the effect of mb on the dissolution of Cu-substituted borosilicate glass at low temperature and near neutral pH conditions, using batch dissolution experiments. Methanobactin promotes the dissolution of Cu-substituted glasses at rates faster than control experiments. Glasses with lower concentrations of copper (80 p.p.m.) or no copper are dissolved more rapidly by mb than those with more abundant copper (800 p.p.m.). Within the first 2 h of reaction, mb sorption onto glass surfaces limits mass transfer of Cu into solution, and at higher concentrations (100 ∝ mol) of the ligand, inhibits dissolution rates of all glass formulations. These results suggest that both the concentration of mb in solution and the solid phase Cu concentration impact silicate weathering rates and related cycling of carbon in near-surface geological settings.

The abundance of six tetracycline resistance genes tet(O), tet(Q), tet(W), tet(M), tet(B) and tet(L), were quantified over time in wastewater lagoons at concentrated animal feeding operations (CAFO) to assess how feedlot operation affects resistance genes in downstream surface waters. Eight lagoons at five cattle feedlots in the Midwestern United States were monitored for 6 months. Resistance and 16S-rRNA gene abundances were quantified using real-time PCR, and physicochemical lagoon conditions, tetracycline levels, and other factors (e.g. feedlot size and weather conditions) were monitored over time. Lagoons were sorted according to antibiotic use practice at each site, and designated as 'no-use', 'mixed-use' or 'high-use' for comparison. High-use lagoons had significantly higher detected resistance gene levels (tet(R); 2.8 x 10(6) copies ml(-1)) relative to no-use lagoons (5.1 x 10(3) copies ml(-1); P < 0.01) and mixed-use lagoons (7.3 x 10(5) copies ml(-1); P = 0.076). Bivariate correlation analysis on pooled data (n = 54) confirmed that tet(R) level strongly correlated with feedlot area (r = 0.67, P < 0.01) and 'total' bacterial 16S-rRNA gene level in each lagoon (r = 0.51, P < 0.01), which are both characteristic of large CAFOs. tet(M) was the most commonly detected gene, both in absolute number and normalized to 16S-rRNA gene level, although tet(O), tet(Q) and tet(W) levels were also high in the mixed and high-use lagoons. Finally, resistance gene levels were highly seasonal with abundances being 10-100 times greater in the autumn versus the summer. Results show that antibiotic use strategy strongly affects both the abundance and seasonal distribution of resistance genes in associated lagoons, which has implications on water quality and feedlot management practices.

Invasive transitional cell carcinoma (TCC) of the urinary bladder responds poorly to medical therapy. Combining platinum chemotherapy with a cyclooxygenase (cox) inhibitor has shown promise against canine TCC, where the disease closely mimics the human condition. A phase II clinical trial of carboplatin combined with the cox inhibitor, piroxicam, was performed in 31 dogs with naturally occurring, histopathologically confirmed, measurable TCC. Complete tumour staging was performed before and at 6-week intervals during therapy. Tumour responses in 29 dogs included 11 partial remissions, 13 stable disease and five progressive disease. Two of the 31 dogs were withdrawn prior to the re-staging of the tumour. Gastrointestinal toxicity was observed in 23 dogs. Hematologic toxicity was noted in 11 dogs. The median survival was 161 days from first carboplatin treatment to death. In conclusion, carboplatin/piroxicam induced remission in 40% of dogs providing evidence that a cox inhibitor enhances the antitumour activity of carboplatin. The frequent toxicity and limited survival, however, do not support the use of this specific protocol against TCC.

The formation of scales and feathers in reptiles and birds has fascinated biologists for decades. How might the developmental processes involved in the evolution of the amniote ectoderm be interpreted to shed light on the evolution of integumental appendages? An Evo-Devo approach to this question is proving essential to understand the observation that there is homology between the transient embryonic layers covering the scale epidermis of alligators and birds and the epidermal cell populations of embryonic feather filaments. Whereas the embryonic layers of scutate scales are sloughed off at hatching, that their homologues persist in feathers demonstrates that the predecessors of birds took advantage of the ability of their ectoderm to generate embryonic layers by recruiting them to make the epidermis of the embryonic feather filament. Furthermore, observations on mutant chickens with altered scale and feather development (Abbott and Asmundson [1957] J. Hered. 18:63-70; Abbott [1965] Poult. Sci. 44:1347; Abbott [1967] Methods in developmental biology. New York: Thomas Y. Crowell) suggest that the ectodermal placodes of feathers, which direct the formation of unique dermal condensations and subsequently appendage outgrowth, provided the mechanism by which the developmental processes generating the embryonic layers diverged during evolution to support the morphogenesis of the epidermis of the primitive feather filament with its barb ridges.

Cross Reservoir, a small mesotrophic reservoir located at the University of Kansas Ecological Reserves (Kansas, USA), contained a dense metalimnetic community of algae and photosynthetic bacteria between early July and late October 1997-1999. Within this community, various Cryptomonas species, primarily C. erosa (Ehrenberg), C. erosa var. reflexa (Marsson), and C. rostratisformis (Skuja), diurnally migrated as indicated by in situ fluorescence monitoring and direct phytoplankton enumeration. The Cryptomonas spp. typically resided near the oxic-anoxic boundary of the water column; however, they actively migrated upward during the day and descended to lower anoxic locations at night, apparently responding to diurnal changes in their local habitat. Their nocturnal environment had moderate levels of sulfide, elevated secondary nutrients, and a community of anoxygenic phototrophic bacteria, whereas their daytime environment had higher light, lower nutrients, and no local photosynthetic bacteria. Monitoring indicated that the Cryptomonas spp. migration was generally linked to daily variations in absolute light intensity (e. g. sunny vs. cloudy days) and the level of other potentially growth-limiting resources, particularly nitrogen and phosphorus. However, further analyses showed that the primary factor that determined whether the Cryptomonas spp. migrated or not on a given day was the slope of the light gradient immediately above the Cryptomonas spp. peak.

The discovery that structurally unique ''filamentous integumentary appendages'' are associated with several different non-avian dinosaurs continues to stimulate the development of models to explain the evolutionary origin of feathers. Taking the phylogenetic relationships of the non-avian dinosaurs into consideration, some models propose that the ''filamentous integumentary appendages'' represent intermediate stages in the sequential evolution of feathers. Here we present observations on a unique integumentary structure, the bristle of the wild turkey beard, and suggest that this non-feather appendage provides another explanation for some of the ''filamentous integumentary appendages.'' Unlike feathers, beard bristles grow continuously from finger-like outgrows of the integument lacking follicles. We find that these beard bristles, which show simple branching, are hollow, distally, and express the feather-type b keratins. The significance of these observations to explanations for the evolution of archosaurian integumentary appendages is discussed. J. Exp. Zool. (Mol. Dev. Evol.) 297B: 27-34, 2003. r 2003 Wiley-Liss, Inc.

A retrospective study of 43 dogs with anal sac adenocarcinoma (ASAC) was performed to characterize the clinical presentation and response to treatment. Clinical signs at presentation varied considerably, with signs related either to sublumbar nodal metastasis (tenesmus or constipation) or hypercalcemia (polyuria-polydipsia and anorexia) being the most frequent findings. At the time of presentation, 23 (53%) dogs had hypercalcemia and 34 (79%) had metastases, with the regional lymph nodes (31 dogs, 72%) being the most common site of metastasis. A variety of chemotherapeutic agents were administered, with partial remission (PR) recorded in 4 of 13 (31%) dogs treated with cisplatin and in 1 of 3 (33%) dogs treated with carboplatin. The median survival for all dogs was 6 months (range, 2 days-41 months). There was no statistical association between the presence of hypercalcemia and survival, although the power of the study to detect an increase in survival of 3 months was low (.33). We conclude that platinum chemotherapy has antitumor activity in canine apocrine gland carcinoma and that further study of these agents is warranted.

We report small fibrous structures associated with a new specimen of Shuvuuia deserti, which we hypothesize are remnants of feather-like epidermal appendages. Multiple analyses suggest that these structures are epidermally derived and contain epitopes consistent with β-keratin, a protein expressed only in extant “reptiles” and birds. Morphological, microscopic, mass spectrometric, and immunohistochemical studies are consistent with the interpretation that these structures are related to feathers. These data suggest that proteinaceous components may survive across geological time and support the view that alvarezsaurids (Shuvuuia and its allies) are either a lineage of birds or are a lineage phylogenetically close to them. J. Exp. Zool. (Mol. Dev. Evol.) 285:146–157, 1999. © 1999 Wiley-Liss, Inc.

Twenty-seven dogs with naturally occurring mast cell tumors were treated with weekly i.v. injections of vincristine (0.75 mg/m2) for 4 treatments. Two dogs (7%) had a partial response. Nine dogs (32%) had treatment stopped prematurely because of toxicity or a perceived deterioration in their quality of life. We conclude that vincristine is ineffective as a sole treatment for measurable mast cell tumors in dogs and produces an undesirable number of adverse reactions.

Because dogs with bladder cancer often have advanced disease at the time of diagnosis, the identification and use of a tumor marker that could facilitate earlier diagnosis is a valid approach to improve prognosis. The objective of this study was to determine if urine concentrations of the proangiogenic peptide, basic fibroblast growth factor (bFGF), are high in dogs with bladder cancer compared with normal dogs and dogs with urinary tract infection. We used a commercially available enzyme-linked immunosorbent assay test kit to quantitate bFGF in the urine of 17 normal dogs, 10 dogs with urinary tract infection, and 7 dogs with locally active transitional cell carcinoma of the urinary bladder. In normal dogs, the median urine bFGF concentration was 2.23 ng/g creatinine (quartile range, 1.53 to 5.12 ng/g creatinine). The median urine bFGF concentration in dogs with urinary tract infection did not differ significantly from normal dogs. Dogs with bladder cancer had significantly higher urine bFGF concentrations than normal dogs (P < .002) and dogs with infection (P < .02). The median urine bFGF concentration in dogs with transitional cell carcinoma was 9.86 ng/g creatinine (quartile range, 7.40 to 21.63 ng/g creatinine). Six of 7 dogs with bladder cancer had urine bFGF concentrations that were up to 7.4 times the 90th percentile value for normal dogs. Only 1 of 10 dogs with infection had a urine bFGF concentration that exceeded the 90th percentile of normal. These data suggest that canine bladder cancers export bFGF, and that urine bFGF may be useful as a diagnostic tumor marker or noninvasive indicator of treatment response.

Information concerning the frequency of seasonal and monthly heat unit accumulations is essential in a variety of applications ranging from the selection of crop varieties to the scheduling of crop management practices. More importantly, differences in heat unit calculation methods and temperature observations practices between the USA and Canada have impeded the transfer of knowledge regarding variety trials across the border. Recently, a regionwide climatology of heat unit statistics has been developed for the northeastern USA and southeastern Canada. Using a high-quality set of climatic data, this climatology depicts the regional distribution of seasonal heat units for five percentile levels (10th, 25th, 50th, 75th, and 90th) and three calculation methods (base 50, 50-86 method, and corn heat units [CHU]). In addition, median monthly heat unit accumulations and median days until corn (Zea mays L.) emergence and the five-leaf stage in corn are also presented. This study details the procedures used in developing the climatology. In particular, efforts to assure the comparability of heat unit accumulations derived from different observation times and practices are discussed. The resulting heat unit maps across the USA indicate a general northeast-southwest alignment of the heat unit isopleths. This pattern mirrors the orientation of the Atlantic Coast and Appalachian Mountains. In Canada, a similar isopleth pattern is indicated in the interlake region of Ontario. Comparing heat unit accumulations across the U.S.-Canadian border, suggests that crop varieties (particularly corn and soybean [Glycine max (L.) Merr.]) bred to meet maturity requirements in southern Ontario, can supplement varieties currently grown across much of New York, northwestern Pennsylvania, and parts of central New England.

Tumor-associated hypoglycemia has been reported in dogs with pancreatic beta-cell tumors, hepatic tumors, and, rarely, with other neoplasms. This article describes 4 dogs with marked hypoglycemia associated with smooth muscle tumors (jejunal leiomyoma, gastric leiomyoma and leiomyosarcoma, and splenic leiomyosarcoma). Presenting clinical signs included grand mal seizures, lethargy, weakness, ataxia, and, in 1 dog, polyuria/polydipsia. The serum insulin concentration was low in 1 dog and normal in the other dog evaluated. Immunohistochemical staining for insulin was negative in the 4 tumors; the 3 tumors arising from the stomach and jejunum stained diffusely positive for glucagon. Blood glucose concentrations rapidly returned to normal after complete surgical resection of the tumors, and clinical signs associated with hypoglycemia resolved. Long-term follow-up available in 3 of the 4 dogs found no recurrence of clinical signs related to hypoglycemia at 15, 31, and 38 months after surgery, respectively.

Purpose: Ultrasound (US) is a noninvasive, nonradiographic imaging technique with high spatial and temporal resolution that can be used for localizing soft-tissue structures and tumors in real-time during radiotherapy (inter- and intra-fraction). A detailed methodology integrating 3D-US within RT is presented. This method is easier to adopt into current treatment protocol than current US based systems and reduces user variability for image acquisition, thus eliminating transducer induced changes that limit CT planning system. Methods: We designed an in-house integrated US manipulator and platform to relate CT, 3D-US and linear accelerator coordinate systems. To validate the platform, an agar-based phantom with measured densities and speed-of-sound consistent with tissues surrounding the bladder, was rotated (0–45°) resulting in translations (up to 55mm) relative to the CT and US coordinate systems. After acquiring and integrating CT and US images into the treatment planning system, US-to-US and US-to-CT images were co-registered to re-align the phantom relative to the linear accelerator. Errors in the transformation matrix components were calculate to determine precision of this method under different patient positions. Results: Statistical errors from US-US registrations for different patient orientations ranged from 0.06–1.66mm for x, y, and z translational components, and 0.00–1.05° for rotational components. Statistical errors from US-CT registrations were 0.23–1.18mm for the x, y and z translational components, and 0.08–2.52° for the rotational components. Conclusion: Based on our result, this is consistent with currently used techniques for positioning prostate patients if couch re-positioning is less than a 5 degree rotation. We are now testing this on a dog patient to obtain both inter and intra-fractional positional errors. Additional design considerations include the future use of ultrasound-based functionality (photoacoustics, radioacoustics, Doppler) to monitor blood flow and hypoxia and/or in-vivo dosimetry for applications in other therapeutic techniques, such as hyperthermia, anti-angiogenesis, and particle therapy.

The transient embryonic layers primarily composed of a periderm and subperiderm cover most regions of the chick embryo and are the first suprabasal cell layers covering the body ectoderm. This study presents evidence for regional variation in the expression of beta keratin in the embryonic layers. Here we show that the embryonic layers covering the anterior metatarsal region of the chicken hindlimb (scutate scale forming region) produce several members of the beta keratin family of polypeptides, designated beta (beta) 1-7. These specific polypeptides are later expressed in this region exclusively in the thick, cornified beta strata of mature scutate scales. In contrast to this sequence of events, the embryonic layers overlying the epidermis of the ventral foot pad (reticulate scale-forming region) and those covering the epidermis in apteric regions of the body produce beta keratin polypeptides beta 1-3 and beta 2,3, respectively, but no subsequent expression of these proteins occurs in the mature epidermises of these regions. Furthermore, we find that the embryonic layers of the skin overlying the anterior metatarsal region of birds homozygous for the mutation "scaleless" (sc/sc), which completely lack scutate scales, produce the same members of the beta keratin family, beta 1-7, as the embryonic layers and beta strata of normal scutate scales. Thus, the accumulation of specific beta keratin polypeptides in the developing anterior metatarsal region appears to occur in two distinct phases; first, an early region-specific expression in cells of the embryonic layers followed by a second phase of expression which occurs in conjunction with appendage morphogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

K-Ras mutant fraction (MF) was measured to examine the default assumption of low-dose linearity in the benzo[a]pyrene (B[a]P) mutational response. Groups of 10 male A/J mice (7- to 9-weeks old) received a single i.p. injection of 0, 0.05, 0.5, 5, or 50 mg/kg B[a]P and were sacrificed 28 days after treatment. K-Ras codon 12 TGT and GAT MFs in lung DNAs were measured using Allele-specific Competitive Blocker-PCR (ACB-PCR). The K-Ras codon 12 TGT geometric mean MF was 3.88 × 10−4 in controls, indicating an average of 1 mutation in every ∼1,288 lung cells. The K-Ras codon 12 TGT geometric mean MFs were as follows: 3.56 × 10−4; 6.19 × 10−4; 2.02 × 10−3, and 3.50 × 10−3 for the 0.05, 0.5, 5, and 50 mg/kg B[a]P treatment groups, respectively. The 5 and 50 mg/kg dose groups had TGT MFs significantly higher than did controls. Although 10−5 is considered as the limit of accurate ACB-PCR quantitation, K-Ras codon 12 GAT geometric mean MFs were as follows: 8.38 × 10−7, 1.47 × 10−6, 2.19 × 10−6, 5.71 × 10−6, and 8.99 × 10−6 for the 0, 0.05, 0.5, 5, and 50 mg/kg B[a]P treatment groups, respectively. The K-Ras TGT and GAT MFs increased in a B[a]P-dose-dependent manner, with response approximately linear over the 0.05 to 5 mg/kg dose range. K-Ras MF increased with B[a]P adduct burden measured for identical doses in a separate study. Thus, ACB-PCR may be useful in characterizing the shape of a dose-response curve at low doses and establishing relationships between DNA adducts and tumor-associated mutations. Environ. Mol. Mutagen. 2010. Published 2009 Wiley-Liss, Inc.

The use of moulds to facilitate the placement and formation of cores on broken-down teeth prior to crown construction is described. The moulds are made of a transparent thermoplastic material and are designed in a number of configurations according to the tooth to be restored. They produce cores of a predetermined taper and an axially corrugated surface.

Rotation-mediated aggregation was used to test the capacity of early embryonic tongue cells from different regions of the tongue to reorganize histotypically and terminally differentiate in vitro. Cells dissociated from the anterior ventral (AV) or posterior ventral (PV) surface of the 12 day embryonic tongue were cultured 6 days, fixed, and embedded in paraffin. Indirect immunofluorescence microscopy was used to demonstrate the occurrence and distribution of beta-keratins, the presence of which represented regional and differentiation specific markers of late tongue development. Aggregates of AV cells were organized into a beta-keratin-producing stratified epithelium. Similar PV aggregates formed only an alpha-keratin-producing stratified epithelium. The epithelial cells of these tongue tissues constructs expressed alpha- and beta-keratins in a manner consistent with the temporal and histotypical expression of keratins observed in vivo.

Hindlimb amputation may be necessary in cases of neoplasia, neurogenic atrophy, permanent functional impairment from chronic orthopaedic disease and severe soft tissue injury. Midshaft femoral amputation may not be satisfactory when wide tissue margins are required. This report describes the procedure and the results of two techniques of hindlimb removal. The first disarticulation technique leaves the thigh musculature attached to the body and the second technique is an ‘en bloc’ resection of the rear leg. Five clinical cases leaving the thigh musculature intact and eight clinical cases of en bloc resection are summarised. Indications and complications are discussed. Although not curative in all cases, all owners were satisfied with the end surgical results and functional outcome.

In this report we compare the effect of stimulation of peripheral mononuclear cells (PBMC) by using two monoclonal antibodies (MoAb) directed against the CD2 receptor on T cells or by using autologous erythrocytes (E) which express on their surface lymphocyte function-associated antigen 3 (LFA3), a natural ligand for CD2. The addition of autologous erythrocytes to pokeweed mitogen (PWM)-stimulated PBMC results in the enhancement of polyclonal immunoglobulin synthesis and of antigen-specific B-cell responses. Because B cells lack the CD2 molecule, it can be concluded that their enhanced activity is a consequence of the delivery of activating signals by activated T lymphocytes. When PBMC cultures were stimulated with a pair of anti-CD2 MoAb (Leu5b and VIT13) we were able to induce polyclonal immunoglobulin synthesis, particularly IgM, in cultures supplemented with interleukin 2(IL-2). Specific responses to tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH) were also enhanced by the addition of autologous E to PWM-stimulated PBMC. Significant anti-TT responses were observed in cultures stimulated with E + TT + IL-2. In contrast, stimulation of PBMC with VIT13 + Leu5b + IL-2 + antigen was not effective in inducing anti-TT antibody and only weakly effective in inducing anti-KLH antibodies. Replacing Leu5b by anti-CD3 had no effect on the induction of specific antibody responses; in contrast, replacement of Leu5b by E enhanced anti-TT antibody production while the effect on polyclonal production of IgM was minimal. Therefore, it appears that the signal delivered by the association of CD2 with LFA3 is a better potentiating signal for specific B-cell responses than the signal delivered by pairs of MoAb to different epitopes of CD2 or to CD2 and CD3 epitopes.

Introduction: Mycobacterial cell wall-DNA complex (MCC) is a bifunctional anticancer agent that induces cancer cell apoptosis and stimulates cytokine synthesis by immune cells. Intravesical MCC is currently being evaluated in humans with high-grade urinary bladder cancer. Evaluation of MCC in dogs with transitional cell carcinoma (TCC) will allow mechanistic studies in a natural animal model of TCC, and a potentially beneficial therapy for dogs with this cancer. In this study, we have determined the anticancer activity of MCC against canine TCC cells in vitro. Methods: Canine TCC cells (K9TCC cell line) were incubated with MCC (0.05–100 μg/ml, 0.5–72 hours). Cellular proliferation was measured by MTT reduction. Cell cycle was analyzed by flow cytometry with propidium iodide. Apoptosis was identified by flow cytometry using anti-active-caspase-3/PE and anti-cleaved-PARP/FITC antibodies. Apoptosis-inducing activity of 100 μg/ml MCC in combination with piroxicam (0.1–1.0 uM) was evaluated. Results: MCC inhibited K9TCC cell proliferation in a concentration-dependent manner (maximal activity – 45% at 100 μg/ml MCC) in association with the presence of activated caspase-3 and cleaved PARP. Inhibition of proliferation and apoptosis-inducing activities of MCC were independent of cell cycle phase. A thirty-minute exposure of MCC was sufficient for optimal activity. Piroxicam (0.5 uM) enhanced apoptosis-inducing activity of MCC. Conclusions: MCC induces apoptosis in K9TCC cells. This activity is potentiated by piroxicam. Following positive results in vitro, in vivo studies have been initiated. One dog, treated to date, has had a minor reduction in tumor volume following the first course of treatment with no treatment-related toxicity.

Common carp (Cyprinus carpio) were treated in aquatic mesocosms with a single pulse of the herbicides atrazine or alachlor to study the bioavailability and biological activity of these herbicides using molecular indicators: Liver vitellogenin gene expression in male fish for estrogenic activity, liver cytochrome P4501A1 gene expression, and DNA damage in blood cells using the single-cell gel electrophoresis method. Both alachlor and atrazine showed dose-related increases in DNA strand breaks at environmentally relevant concentrations (

Aquifers found in glacial buried valleys are a major source of good-quality ground water in northeastern Kansas. The extent and character of many of these deposits are not precisely known, so a detailed study of the buried valleys was undertaken. Test drilling, Landsat imagery, shallow-earth temperature measurements, seismic refraction, surface electrical resistivity, and gravity data were used to evaluate two sites in Nemaha and Jefferson Counties. Tonal patterns on springtime Landsat imagery and winter/summer anomalies in shallow-earth temperatures were quick and inexpensive methods for locating some glacial buried aquifers and suggested areas for more intensive field studies. Reversed seismic refraction and resistivity surveys were generally reliable indicators of the presence or absence of glacial buried valleys, with most depth determinations being within 25% of test-drilling results. The effectiveness of expensive test-hole drilling was greatly increased by integrating remote sensing, shallow-earth temperature, seismic, and resistivity techniques in the two buried valley test areas. A gravity profile allowed precise definition of the extent of one of the channels after the other techniques had been used for general information.

Composite complete-incomplete (C-I) block designs are formed by combining complete blocks of size t units with balanced incomplete blocks of k units (1 ≤ k < t) resulting in blocks of size t+k units. In sensory experiments, composite C-I block designs have been shown to be more efficient than the standard complete block designs. Replication of the blocks in these C-I block designs permits accurate interpretation of panelist X treatment interaction effects. Also, the formulae for calculating estimates of the treatments, panelists, and interaction effects are simpler in form with the replicated C-I designs than the corresponding formulae with the unreplicated C-I block designs. The analysis of an experiment involving the rating of flavor of three strawberry preserves using a replicated C-I block design is presented.

Forty-one dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin (cis-diamminedichloroplatinum, Platinol, Bristol Laboratories, Syracuse, NY 13221-4755) as a single agent at a dosage of 60 mg/m2 given intravenously at 3-week intervals. In an attempt to avoid renal toxicity of cisplatin, saline diuresis was induced and maintained for 4 hours before and 2 hours following cisplatin administration. The dogs received one to ten doses of cisplatin. To determine response to therapy and to monitor toxicity of the drug, the dogs were evaluated with physical examinations including tumor measurements, radiography, complete blood counts, platelet counts, urinalyses, serum urea nitrogen concentrations, and serum creatinine concentrations. An overall response rate of 19% was observed. Complete remission occurred in one of 11 dogs with squamous cell carcinomas and one of one dog with a mediastinal undifferentiated carcinoma. Partial remissions were documented in one of 11 dogs with squamous cell carcinomas, two of three dogs with metastatic osteosarcomas, one of three dogs with nasal adenocarcinomas, and one of one dog with a thyroid adenocarcinoma. Toxic side effects were primarily gastrointestinal in nature, with vomiting occurring 1-6 hours after cisplatin administration in 27 of 41 dogs. Severe anorexia occurred in three dogs, and hemorrhagic diarrhea was observed in one dog. One dog developed grand mal seizures and died 3 hours following therapy. Granulocytopenia was documented in six dogs, and thrombocytopenia was observed in four dogs. One dog showed an increase in serum urea nitrogen and creatinine concentrations, but this patient had known pre-existing renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper reports on the development of a mathematical model for forecasting energy development in the Yellowstone study area for the years 1985 and 2000, and determining the associated economic demands for water, land, labor, capital, and mineral resources. The study was prepared for use by the Missouri River Basin Commission in conducting a comprehensive, ''Level B'' planning study of the water and related land resources in the Yellowstone River Basin. The study results indicate that the amount of coal development in the Yellowstone study area will depend primarily upon state and federal energy policies and regulations. Policies related to slurry pipeline transportation of coal will be particularly important in determining the level and pattern of future energy development in the area. Coal production under the ''most probable'' scenario is expected to increase from about 40 million tons in 1976 to 163 million tons per year by 1985, and 513 million tons in the year 2000. Consumptive water use for energy development in the study area could be as much as 556,000 acre-feet per year by the year 2000 (under the high scenario). A parametric analysis was conducted on the 1985 most probably scenario to determine the influence on themore » study results of variations in the delivered price of water. Water requirements were reduced by nearly one-fourth as water costs increased from zero to over $750 per acre-foot.« less

SYNOPSIS The aim of this contribution is twofold: first, a reply is given to Elmore and Tursky.1 who hypothesized that temporal pulse amplitude biofeedback (TPA) works on the basis of sympathetic activation. Contrary to this point of view, some data are reported supporting the opposite tendency: i.e. sympathetic deactivation. Secondly, based on the first part of this article, a new hypothesis is formulated with the intention of explaining temporal vasoconstriction simultaneously found with digital vasodilation and handtemperature increase during handwarming biofeedback (HTB) resp. during volitional handwarming/relaxation.1,11 This new hypothesis postulates that temporal vasoconstriction occurs during handwarming/relaxation due to the fact that peripheral extracranial scalp and face arterioles dilate. As a result, blood and oxygen supply as well as carbon dioxide release is increased, which leads in turn to a reduction in arteriolar ischemia, hypoxia and acidosis. The improved blood delivery from the temporal arteries to the extracranial arterioles and tissue provokes a relative degree of vasoconstriction of the temporal arteries.

We have determined the distribution of alpha and beta keratins in avian scutate scales using SDS-PAGE and indirect immunofluorescence with non-cross-reacting rabbit antisera prepared to both alpha and beta keratins. Contrary to previous studies, we find that alpha keratin is definitely present in the epidermis of the outer scale surface as well as that of the inner surface and hinge region of the scale. In fact, all six alpha keratin polypeptides found in the whole scale epidermis are also present in epidermis taken exclusively from the outer scale surface. Three of these polypeptides demonstrate a specific enrichment in the epidermis of the outer scale surface when compared to the polypeptides of the entire scale epidermis. Immunofluorescence studies specifically localize the alpha keratins of the outer scale epidermis in the Stratum Basale and Stratum Intermedium, but the beta keratins are restricted to the Stratum Intermedium and Stratum Intermedium and Stratum Corneum.

The functional activity of monocytes in human disease and the role of this particular cell type in host defense is a matter of current interest. Among several assays for monocyte function, an antibody-dependent cellular cytotoxicity microassay is regarded as a convenient test system in which monocytes of a Ficoll-Hypaque-separated mononuclear cell fraction act as effector cells and consequently lyse 51Cr-labeled, antibody-coated human erythrocytes. This assay was applied to a total of 35 individuals: 20 patients with Stage I melanoma and 15 healthy control subjects. All melanoma cases were treated by means of excision of the primary lesions and subsequent regional lymphadenectomy. Ten patients were selected at random and received additional adjuvant BCG immunotherapy for periods of 9.4 +/- 1.7 months. The mean percentage of 51Cr released in melanoma patients not receiving BCG was significantly lower (P less than 0.01%) than that in healthy control subjects. Monocyte numbers, as evaluated by means of nonspecific esterase staining, were not statistically significantly different.

Sonographic evaluation of the pancreas was performed in ten healthy research dogs following intraperitoneal fluid administration. Physiological saline solution was aseptically introduced into the peritoneal cavity of each dog to create an acoustic window that would facilitate sonographic delineation of normal pancreatic tissues. Abdominal ultrasound examinations were performed in all dogs before and after the production of the diagnostic hydroperitoneum. Sonograms of the pancreas and other abdominal organs were scored on the basis of image clarity by experienced and novice ultrasonographers. Statistical analysis was then used to compare the effectiveness of each preparation method. A significant difference (P < 0.05) was established between the scores from the diagnostic hydroperitoneum sonograms and the baseline scans performed without intraperitoneal fluid placement. Sonographic visualization scores for the pancreas and other abdominal organs were increased following production of the diagnostic hydroperitoneum. These results indicate that the technique of diagnostic hydroperitoneum will significantly improve ultrasonographic visualization of the pancreas, and may prove useful in the diagnosis of canine pancreatic disease.

Retinoic acid-induced transformation of reticulate scales to feather-like structures (Dhouailly and Hardy, '78) provides a useful model to study biochemical differentiation in avian skin. In this study, immunofluorescent analysis of reticulate scale-feathers (RSFs) indicates that they contain beta keratin in feather barbs and, thus, are true feathers, biochemically. Epidermal cells that would otherwise produce only alpha keratin in reticulate scales are induced to reorganize and differentiate into barb ridge cells that accumulate feather beta keratins. The mechanism for these dramatic morphological and biosynthetic responses to retinoic acid is unknown.

Using a rosette technique with IgM coated bovine red blood cells (EA-IgM) receptors for IgM can be demonstrated on human B-lymphocytes. While in the peripheral blood B cells with IgM receptors are found only occasionally, between 7 and 33%, mean 16%, of tonsil B-lymphocytes exhibit receptors for IgM. This was shown in double marker studies using EA-IgM for the demonstration of IgM receptors and fluorochrome labelled conjugates for the demonstration of S-IgD, S-IgM and B cell antigens. These receptors are specific for IgM, they can be completely blocked by IgM-anti OVA complexes and partially by free IgM, but not at all by aggregated human IgG. They are sensitive to trypsin and pronase but reconstitute after further incubation at 37 degrees C. These data show that not only T and CLL cells but also some normal B-lymphocytes have receptors for IgM. We favour the view that CLL lymphocytes may derive from these B-lymphocytes, which may represent a certain maturation step in B cell development.