Progress in High-Speed Spin Testing of Superconducting Wire and Tapes for High-Field NMR Magnet Qualification.

This paper summarizes the status of a 3-year, NIH-funded research project to study the strength of high temperature superconductors under high circumferential hoop stress, in order to qualify these materials for high-field (> 1 GHz-class NMR magnets. The unique approach presented here is to spin test coils at high rotational speeds, approaching 100,000 rpm, in order to induce the necessary hoop stress. Thermal strain compatibility between the Bi-2212 wire and Inconel wire has been qualified, including thermal cycling. Assembly and testing of the first low-speed (< 30,000 rpm) rotor is now in process, and the design of second, higher speed (> 60,000 rpm) rotor, is also underway.

Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis): Severity and Risk Factors.

Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum AA (SAA) from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli (98% [n= 78 of 80] vs 56% [n= 45], respectively;P< .0001), and medullary deposition was more commonly severe (19% [n= 20 of 105]) as compared with glomeruli (7% [n= 7];P= .01). Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes as compared with free-ranging foxes (ORs = 3.2, 3.7, respectively; overall P= .05) and for females as compared with males (OR = 2.9;P= .05). Multivariable logistic regression revealed that independent risk factors for amyloid development were increasing age class (OR = 3.8;P< .0001), San Clemente Island subspecies versus San Nicolas Island subspecies (OR = 5.3;P= .0003), captivity (OR = 5.1;P= .0001), and nephritis (OR = 2.3;P= .01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis.

Leukoencephalomyelopathy of mature captive cheetahs and other large felids: a novel neurodegenerative disease that came and went?

A novel leukoencephalomyelopathy was identified in 73 mature male and female large captive felids between 1994 and 2005. While the majority of identified cases occurred in cheetahs (Acinonyx jubatus), the disease was also found in members of 2 other subfamilies of Felidae: 1 generic tiger (Panthera tigris) and 2 Florida panthers (Puma concolor coryi). The median age at time of death was 12 years, and all but 1 cheetah were housed in the United States. Characteristic clinical history included progressive loss of vision leading to blindness, disorientation, and/or difficulty eating. Neurologic deficits progressed at a variable rate over days to years. Mild to severe bilateral degenerative lesions were present in the cerebral white matter and variably and to a lesser degree in the white matter of the brain stem and spinal cord. Astrocytosis and swelling of myelin sheaths progressed to total white matter degeneration and cavitation. Large, bizarre reactive astrocytes are a consistent histopathologic feature of this condition. The cause of the severe white matter degeneration in these captive felids remains unknown; the lesions were not typical of any known neurotoxicoses, direct effects of or reactions to infectious diseases, or nutritional deficiencies. Leukoencephalomyelopathy was identified in 70 cheetahs, 1 tiger, and 2 panthers over an 11-year period, and to our knowledge, cases have ceased without planned intervention. Given what is known about the epidemiology of the disease and morphology of the lesions, an environmental or husbandry-associated source of neurotoxicity is suspected.

Characterization of the gastric immune response in cheetahs (Acinonyx jubatus) with Helicobacter-associated gastritis.

Captive cheetahs have an unusually severe progressive gastritis that is not present in wild cheetahs infected with the same strains of Helicobacter. This gastritis, when severe, has florid lymphocyte and plasma cell infiltrates in the epithelium and lamina propria with gland destruction, parietal cell loss, and, in some cases, lymphoid follicles. The local gastric immune response was characterized by immunohistochemistry in 21 cheetahs with varying degrees of gastritis. The character of the response was similar among types of gastritis except that cheetahs with severe gastritis had increased numbers (up to 70%) of lamina proprial CD79a+CD21- B cells. CD3+CD4+ T cells were present in the lamina propria, and CD3+CD8α+ T cells were within the glandular epithelium. Lymphoid aggregates had follicular differentiation with a central core of CD79a+/CD45R+ B cells and with an outer zone of CD3+ T cells that expressed both CD4 and CD8 antigens. MHC II antigens were diffusely expressed throughout the glandular and superficial epithelium. No cheetah had evidence of autoantibodies against the gastric mucosa when gastric samples from 30 cheetahs with different degrees of gastritis were incubated with autologous and heterologous serum. These findings indicate that T-cell distribution in cheetahs is qualitatively similar to that in other species infected with Helicobacter but that large numbers of lamina propria activated B cells and plasma cells did distinguish cheetahs with severe gastritis. Further research is needed to determine whether alterations in the Th1:Th2 balance are the cause of this more plasmacytic response in some cheetahs.

The value of biomedical research training for veterinary anatomic and clinical pathologists.

Veterinary pathologists traditionally have been actively engaged in research as principal investigators and as collaborators. Pathologists frequently obtain advanced training in research; however, it appears that in the last 10 years there has been a reversal of a previous trend toward increasing numbers of pathologists obtaining PhD degrees. This has arisen despite an established shortage of veterinarians engaged in research. This article evaluates the benefits of research training for individual pathologists, including a wide spectrum of professional opportunities and additional skill development beyond that usually provided by diagnostic pathology training alone. Various training models are discussed, including combined and sequential diagnostic residency and research degree training as well as the nondegree research fellowship programs more commonly pursued in human medicine. Best-practice recommendations for program infrastructure, mentorship, time management, and a team approach to research and research training are advocated to facilitate the development of successful programs and to encourage a continued emphasis on integrated training for pathologists as both clinical diagnosticians and experimentalists. This article is intended to help prospective and active pathology trainees, their mentors, and educational administrators optimize opportunities to ensure the future vitality of veterinary pathologists, and their contributions, in basic and applied research.

Naturally occurring and melengestrol acetate-associated reproductive tract lesions in zoo canids.

As husbandry practices have improved, safe and effective contraception for captive wildlife management has become a necessity. Melengestrol acetate (MGA), a synthetic progestin, is highly effective and has been used in many zoo species. Long-term use of MGA has been associated with uterine lesions in zoo felids, but effects in zoo canids have not been evaluated. This retrospective study documented spontaneously occurring lesions and investigated the impact of MGA on the reproductive health of zoo canids. Reproductive tracts from adult females were submitted by US zoos to the Association of Zoos & Aquariums' Wildlife Contraception Center Health Surveillance Program. Reproductive tracts were sampled and processed for histopathologic examination following standard protocols. Microscopic evaluations were performed without prior knowledge of MGA treatment status. Prevalence of uterine lesions was evaluated and compared between MGA-treated animals (n = 20) and control (untreated) animals (n = 61). Common lesions within the study population as a whole included endometrial hyperplasia (predominantly cystic) (53%), hydrometra (33%), and adenomyosis (25%). Treatment with MGA was a risk factor for endometrial hyperplasia, hydrometra, fibrosis, and adenomyosis. Uterine mineralization occurred exclusively in MGA-treated animals. Results indicate that MGA contraception can lead to lesions that may permanently impair the fertility of females. Therefore, if long-term contraception of zoo canids is necessary, the use of alternate methods of reproductive control such as gonadotropin-releasing hormone (GnRH) analogs or GnRH vaccines that reduce gonadal hormone exposure should be pursued.

Comparative histopathology and antibody responses of non-Tritrichomonas foetus trichomonad and Tritrichomonas foetus genital infections in virgin heifers.

The potential pathogenicity of non-Tritrichomonas foetus trichomonads (NTfTs) recently isolated from the prepuce of virgin bulls is not known. The purpose of this study was to determine the ability of these NTfTs to cause disease in the female reproductive tract relative to T. foetus. Forty-four virgin heifers were experimentally infected intravaginally with either one of two NTfTs (Pentatrichomonas hominis or Tetratrichomonas spp.), T. foetus, or sterile media and cultured weekly from 0 time until slaughter at 8 weeks. Serum and vaginal antibody responses during infection were assessed, and the reproductive tracts were histologically examined, scored, and compared based on numbers of neutrophils, eosinophils, lymphocytes, and plasma cells as well as the qualitative appearance of the reproductive tract. The NTfTs did not persist in the reproductive tract, while T. foetus persisted for at least 6-8 weeks. Further, no vaginal IgA response to infection was found in NTfT-infected and control heifers, but a vaginal IgA response was present in the T. foetus-infected group. Heifers infected with NTfT or controls showed little mucosal inflammatory response compared to T. foetus-infected heifers. Among the trichomonads studied, persistent infection by T. foetus alone seems responsible for uterine inflammatory lesions usually associated with pregnancy loss. The NTfTs studied in this work only transiently infected the vagina and were associated with strictly mild inflammatory changes, which probably do not cause significant disease, i.e., pregnancy loss.

Molecular cloning and sequence analysis of trp-lac fusion deletions.

DNA fragments containing deletions that fuse the trp operon to the lac operon were cloned and the end-points of the fusions were determined. The results from DNA sequence analysis correlated well with those from genetic, biochemical and physiological studies previously reported. The sequence data from this study, in combination with the known properties of these fusion strains, provided information on: (1) the precise lac operon distal boundary of the lac operator; (2) the nature of the trp operon terminator; and (3) the messenger RNA sequences that result in inhibition of lacZ translation initiation in trp-lac fused mRNAs.

lacZ translation initiation mutations.

Sixteen single point mutations near the beginning of the lacZ gene have been isolated and their effect on lacZ expression has been measured. Five mutations were obtained that alter a potential stem-and-loop structure in the messenger RNA that masks the initiation codons. Formation of this stem-and-loop is a result of transcription of DNA sequences introduced during the cloning of the lac regulatory region. The mutations isolated were then moved into a background that deleted this structure. Analysis of these mutations indicated that the secondary structure inhibited lacZ expression 5.8-fold and that either single point mutations or a 9 base-pair deletion could relieve this inhibition completely. In addition, it was found that an A to C transversion in the first base following the initiation codon (in the absence of the inhibitory secondary structure) decreases lacZ expression almost twofold, whereas C to U transitions in the next two positions have negligible effects. Mutations were also obtained that either increase or decrease the length of the Shine-Dalgarno sequence. The effects of these mutations were studied in the presence or absence of the secondary structure that involves the two initiation codons. It was found that when translation initiation was inhibited by the secondary structure, increasing the length of the Shine-Dalgarno sequence increased lacZ expression 2.8-fold and decreasing the length of this sequence reduced lacZ expression 12-fold. When translation initiation was not inhibited by the secondary structure, increasing the length of the Shine-Dalgarno sequence had no effect and decreasing the length of this sequence only reduced lacZ expression sixfold. The mechanistic implications of these results are discussed. Two initiation codons are located in the beginning of the lacZ gene, 7 and 13 bases from the Shine-Dalgarno sequence. NH2-terminal sequence analysis indicated that the majority of the protein synthesized initiate at the first initiation codon in the wild-type lacZ gene (in agreement with results reported previously by J. L. Brown and his colleagues). Upon introduction of sequences that result in a change in the mRNA secondary structure, both initiation codons are used in almost equal amounts. Three mutations and two pseudorevertants were obtained, which are located in the first initiation codon. It was found that when the first initiation codon is changed from AUG to GUG, translation initiation is decreased tenfold at that codon.(ABSTRACT TRUNCATED AT 400 WORDS)

Rabies and African wild dogs in Kenya.

Three packs of African wild dogs (Lycaon pictus) ranging to the north of the Masai Mara National Reserve in southwestern Kenya were monitored from 1988 to 1990. During a six week period (August 2-September 14, 1989), 21 of 23 members of one of these packs died. Histological examination of two brain samples revealed eosinophilic intracytoplasmic inclusions (Negri bodies), supporting a diagnosis of rabies viral encephalitis. An additional brain sample tested positive for rabies with a fluorescent antibody test. Nucleotide sequence of the rabies viral N and G genes from isolates of four African wild dogs (including an individual from Tanzania) indicated that infection was with a viral variant common among domestic dogs in Kenya and Tanzania. A hypothesis linking African wild dog rabies deaths to researcher handling is evaluated and considered implausible.

Protective effect of dietary brussels sprouts against mammary carcinogenesis in Sprague-Dawley rats.

The effect of dietary brussels sprouts (Brassica oleracea, L.) on mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) was studied in Sprague-Dawley female rats. Rats fed a 20% brussels sprouts diet only during the initiation period of carcinogenesis had a palpable mammary tumor incidence of 13%, while those fed a casein-cornstarch semi-purified diet during this initiation period had a tumor incidence of 77% after 15 weeks post DMBA dose. When the rats were switched from the semi-purified diet to the 20% brussels sprouts diet at this time, there appeared to be a regression of small mammary tumors after 6 weeks on this dietary treatment. This regression was transitory since during the final 10 weeks of this 1 year study, 100% of this group of rats developed tumors. The rats fed the 20% brussels sprouts diet during tumor initiation exhibited a 67% incidence of fibroadenomas. The rats fed the semi-purified diet during initiation, but switched later to the brussels sprouts diet, showed over a 90% incidence of adenocarcinomas.

Effect of dietary brussels sprouts with increased selenium content on mammary carcinogenesis in the rat.

Brussels sprouts (Brassica oleracea, L; Jade cross E, hybrid cultivar) were cultivated with inorganic selenium added to the plant growth medium. Sprague-Dawley, female, weanling rats were divided into groups and fed 20% brussels sprouts diets containing either 0.03, 0.58, 1.29, or 6.71 ppm of selenium naturally occurring in the sprouts. These diets were fed 2 weeks before and 2 weeks after a single dose of 7,12-dimethylbenz[a]anthracene (DMBA), and the rats were then placed on a low selenium basal diet for an additional 25 weeks. All brussels sprouts diets reduced the incidence of DMBA-induced mammary carcinogenesis. Increased dietary levels of naturally occurring selenium did not further depress mammary tumorigenesis. The time periods of selenium feeding may have been too brief to observe any additional tumor reductions.

Oxytocin use after previous cesarean: why a higher rate of failed labor trial?

When used for patients undergoing trial of labor after previous cesarean, oxytocin is associated with an increased failure rate. Previous reports have not studied why this occurs. From October 1984 to April 1986, 237 patients with previous cesareans underwent a trial of labor. The delivery outcomes of 73 women who received oxytocin were compared with those of the 164 who did not. Rates were similar for uterine scar dehiscence, uterine rupture, operative vaginal delivery, blood transfusions, endometritis, and low Apgar scores. Successful trial of labor occurred in 68% in the oxytocin group, compared with 89% in the no-oxytocin group. Failed trial of labor was significantly more frequent in patients who received oxytocin for induction of labor than in those who did not. When subjects who received oxytocin were divided into induction (N = 47) and augmentation (N = 26) groups, successful trial of labor occurred in 58% of the former group versus 88% of the latter group. Other characteristics of the augmentation group were spontaneous labor, greater cervical dilation and effacement at initiation of oxytocin, shorter duration of infusion, and lower oxytocin infusion rates. For patients who have had previous cesareans and who desire trial of labor, oxytocin by controlled infusion is safe. Successful trial of labor may be enhanced by awaiting spontaneous labor or inducing with a favorable cervix.

Surgical treatment of biliary cystadenoma. A report of 15 cases.

Mucinous biliary cystadenomas are rare intrahepatic or, less commonly, extrahepatic neoplasms that may produce massive enlargement, hemorrhage, rupture, secondary infection, jaundice, or vena caval obstruction. Radiologic criteria differentiate biliary cystadenomas from more common parasitic or simple cysts. Treatment has included sclerosis, marsupialization, internal drainage, or resection, but without resection the patient is at risk for enlargement, infection, or progression of an unrecognized malignant neoplasm. We report the course of 15 patients who underwent resection for biliary cystadenoma to elucidate the clinical presentation, preoperative evaluation, and surgical treatment. Nine patients had had previous radiologic or surgical intervention other than excision, and complications of sepsis and tumor recurrence had developed. Following complete resection, however, only five postoperative complications were encountered, and no patient experienced recurrence of tumor. Thus, we recommend complete surgical resection as the preferred therapy.

Prevalence of Bartonella infection in wild African lions (Panthera leo) and cheetahs (Acinonyx jubatus).

Bartonella species are emerging pathogens that have been isolated worldwide from humans and other mammals. Our objective was to estimate the prevalence of Bartonella infection in free-ranging African lions (Panthera leo) and cheetahs (Acinonyx jubatus). Blood and/or serum samples were collected from a convenience sample of 113 lions and 74 cheetahs captured in Africa between 1982 and 2002. Whole blood samples available from 58 of the lions and 17 of the cheetahs were cultured for evidence of Bartonella spp., and whole blood from 54 of the 58 lions and 73 of the 74 cheetahs tested for the presence of Bartonella DNA by TaqMan PCR. Serum samples from the 113 lions and 74 cheetahs were tested for the presence of antibodies against Bartonella henselae using an immunofluorescence assay. Three (5.2%) of the 58 lions and one (5.9%) of the 17 cheetahs were bacteremic. Two lions were infected with B. henselae, based on PCR/RFLP of the citrate synthase gene. The third lion and the cheetah were infected with previously unidentified Bartonella strains. Twenty-three percent of the 73 cheetahs and 3.7% of the 54 lions tested by TaqMan PCR were positive for Bartonella spp. B. henselae antibody prevalence was 17% (19/113) for the lions and 31% (23/74) for the cheetahs. The prevalence of seropositivity, bacteremia, and positive TaqMan PCR was not significantly different between sexes and age categories (juvenile versus adult) for both lions and cheetahs. Domestic cats are thus no longer the only known carriers of Bartonella spp. in Africa. Translocation of B. henselae seronegative and TaqMan PCR negative wild felids might be effective in limiting the spread of Bartonella infection.

Genetic characterization of canine distemper virus in Serengeti carnivores.

The lion (Panthera leo) population in the Serengeti ecosystem was recently afflicted by a fatal epidemic involving neurological disease, encephalitis and pneumonia. The cause was identified as canine distemper virus (CDV). Several other species in the Serengeti were also affected. This report presents CDV H and P gene sequences isolated from Serengeti lions (Panthera leo), spotted hyenas (Crocuta crocuta), bat-eared fox (Otocyon megalotis) and domestic dog (Canis familiaris). Sequence analyses demonstrated that the four Serengeti species carry closely related CDV isolates which are genetically distinct from other CDV isolates from various species and locations. The results are consistent with the conclusions that: (1) a particularly virulent strain of CDV emerged among Serengeti carnivores within the last few years; (2) that strain has recognizable shared-derived (synapomorphic) genetic differences in both H and P genes when compared to CDV from other parts of the world; and (3) that the CDV strain has frequently crossed host species among Serengeti carnivores.

Gastric outlet obstruction secondary to pancreatic cancer: surgical vs endoscopic palliation.

BACKGROUND: Gastric outlet obstruction in patients with pancreatic cancer has a grim prognosis. Open surgical bypass is associated with high morbidity, whereas endoscopic duodenal stenting appears to provide better palliation. METHODS: We reviewed the medical records of patients with gastric outlet obstruction secondary to pancreatic carcinoma who were admitted to our clinic between 1 October 1988, and 30 September 1998. The data included stage of disease, American Society of Anesthesiologists (ASA) class, surgical interventions, complications, and survival. RESULTS: A total of 250 patients with pancreatic cancer were identified. Twenty-five of them (10%) had gastric outlet obstruction. Of these 25, 17 were treated with gastrojejunostomy, six had duodenal stenting (Wallstent), and two were resectable. There was no significant difference between the gastrojejunostomy group and the duodenal stenting group in ASA class or stage of disease. For the gastrojejunostomy group, median survival was 64 days (range, 15-167) and postoperative stay in hospital was 15 days (range, 8-39). For the duodenal stenting group, median survival was 110.5 days (range, 42-212) and postoperative stay was 4 days (range, 2-6). Ten patients (58.8%) in the gastrojejunostomy group had delayed gastric emptying. All of the patients in the duodenal stenting group were able to tolerate a soft diet the day after stent placement. Thirty-day mortality in the gastrojejunostomy group was 17.64%; in the duodenal stenting group, it was 0. CONCLUSION: In pancreatic carcinoma patients with gastric outlet obstruction, duodenal stenting results in an earlier discharge from hospital and possibly improved survival.

Inhibition by wine of tumorigenesis induced by ethyl carbamate (urethane) in mice.

Groups of 18-21 male weanling C3H mice were given, as drinking fluid, tap-water, 12% ethanol solution, one of two commercial white wines, or red wine, ad lib. for 41 wk. Ethyl carbamate was added to each of the drinking liquids at levels adjusted to provide average daily ethyl carbamate intakes of 0, 10 or 20 mg/kg body weight. After 41 wk the cumulative survival of the mice given 20 mg ethyl carbamate/kg in water was depressed compared with the mice drinking wines or ethanol solution with this ethyl carbamate level. Both ethanol and wine treatments reduced the incidence of lung Clara-cell adenomas in mice given 10 mg ethyl carbamate/kg and reduced the frequency (number of specific tumours/number of tumour-bearing mice) of both Clara-cell adenomas in mice given 10 mg ethyl carbamate/kg and of alveolar adenomas in mice given 20 mg ethyl carbamate/kg. Wine treatments also reduced the frequency of hepatocellular adenomas compared with those of other treatment groups, and no hepatocellular carcinomas developed in any of the groups given wine, even with the 20-mg/kg ethyl carbamate dose. The incidence of hepatocellular adenomas in the groups given 10 mg ethyl carbamate/kg was, as shown by chi-square analysis, significantly reduced by the ethanol and wine treatments. The mean weight gains of mice on all the wine treatments were lower than those of water-treated mice and this may have been a factor in tumour inhibition; however, it is also possible that wine components other than ethanol may play a role in the inhibition of tumour development.

Studies on fluorescein-III The acid strengths of fluorescein as shown by potentiometric titration.

Potentiometric back-titration of yellow solid fluorescein (H(2)Fl) and of red solid fluorescein in alkali with acid yielded titration curves that were practically identical in shape and position. The end-points at pH 8.5, 5.40 and 3.3 corresponded, respectively, to titration of the excess of standard alkali, and the successive protonations Fl(2-) + H(+) = HFl(-) and HFl(-) + H(+) = H(2)Fl. The pH at the mid-point of the first protonation yielded a value of 6.36 for pK(HFl) (ionic strength 0.10). Because of precipitation of yellow fluorescein during the second protonation step, a value for pK(H(2)Fl) could not be obtained. The total concentration of fluorescein at the first appearance of the precipitate fell on the curve for the solubility of yellow fluorescein as a function of pH. The titrations and the pK values found for the three acid groups of protonated fluorescein (H(3)Fl(+)) have been interpreted on the basis that in water fluorescein exists in only one structural form the yellow zwitterion. Similar back-titrations of alkalinized solutions of yellow or red fluorescein in 50% aqueous ethanol showed that in this medium fluorescein is present in only one form, presumably the quinonoid structure, with much weaker apparent acid functions, pK'(1) = 6.38 and PK'(2) = 7.16 (ionic strength 0.10).