bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Kinase A: Regulation and Receptor‐Mediated Delivery of Antisense Oligonucleotides and Cytotoxic Drugs
Authors: SVESHNIKOV P. G. , GROZDOVA I. D. , NESTEROVA M. V. , SEVERIN E. S.
Published: July 2009

Abstract: Protein kinases help regulate eukaryotic cell division. We investigated the regulation of cAMP‐dependent protein kinase A (PKA) and casein kinase (CK) type I activity in normal cells and in cancer. To assess this activity in biopsies we suggest a new parameter—the ratio of CK activity and total PKA activity divided by cAMP concentration: CK/PKA/cAMP. In 98 samples of colon mucosa in normal, inflamed, polyp, and adenocarcinoma cells, we found this parameter to be fairly constant in normal conditions and increased 10‐fold in colon cancer; the ratio does not depend on the place of biopsy or the patient's age or sex. Experiments with model systems of concanavalin A‐stimulated lymphocytes and regenerating rat liver showed that in normal cell proliferation the parameter increases 2‐3‐fold, as compared to a 30‐fold increase in cancer. Unlike normal cells, malignant cells show CK activation and decrease of cAMP; therefore, PKA activity decreases. This suggests a correlation of CK and PKA activity and significant damage to their regulation at pathological changes of tissue proliferation. To further study concerted CK and PKA regulation we used monoclonal antibodies (mAbs) against cAMP‐dependent protein kinase regulatory subunit RKIIβ. We produced 11 antibodies in three groups: inhibiting, which block cAMP binding with RIIβ and inhibit holoenzyme formation (RS6); activating, which enhance cAMP binding and do not affect holoenzyme formation (RS28); and neutral (RS17). To investigate mAb influence on protein kinase regulation in live cells we permeabilized pheochromocytoma PC12 by digitonin. When used at 5‐μM concentration for 5 min, digitonin allowed us to deliver mAb into PC12 cells at 30‐34‐nM concentration, leaving 68‐75% viable cells. Protein kinase activity was measured within 0.5 and 4 h after incorporation of mAbs into cells. After 30 min incorporation, mAb RS6 blocked PKA activation in PC12 cells under the influence of cAMP; other mAbs showed no effect. mAb RS6 caused a 4‐fold increase of free C subunit activity 4 h after incorporation. mAb RS38 decreased R2C2 activity and did not influence C subunit activity. The change of free C subunit activity caused by mAb incorporation was followed by a synchronized, well‐balanced change of CK type I activity, which suggests a correlation between the two phosphorylation systems of cell proteins.
Role of PTEN, a Lipid Phosphatase Upstream Effector of Protein Kinase B, in Epithelial Thyroid Carcinogenesis
Authors: ENG CHARIS
Published: July 2009

Abstract: Both benign and malignant thyroid disease are well‐established components of Cowden syndrome (CS), an autosomal dominant disorder characterized by multiple hamartomas and breast cancer that may be considered a phakomatosis. The susceptibility gene for CS is PTEN, a tumor suppressor gene on 10q23.3 that encodes a lipid phosphatase that lies upstream of protein kinase B (Akt). Interestingly, Carney complex is also a phakomatosis where multiple endocrine neoplasias are prominent and thyroid cancer might be a rare component. One of its susceptibility genes is the regulatory subunit of protein kinase A. Over the course of the last four years, investigators have found the increasing clinical spectrum of syndromes characterized by germline loss‐of‐function PTEN mutation. In addition to CS, subsets of such disparate syndromes as Bannayan‐Riley‐Ruvalcaba syndrome, Proteus syndrome, and possibly VATER with hydrocephalus and megencephaly with autistic features have been found to have germline PTEN mutations. Paradoxically, somatic intragenic PTEN mutations were rare in uncultured primary epithelial thyroid tumors, although hemizygous deletion occurred in 10‐20% of thyroid adenomas and carcinomas. However, with subsequent study, it was discovered that epigenetic silencing of PTEN and perhaps inappropriate subcellular compartmentalization were two novel mechanisms of PTEN inactivation pertinent in thyroid carcinogenesis. Ectopic expression studies in vitro have borne out the importance of PTEN in the pathogenesis of epithelial thyroid neoplasias.
Cyclic AMP‐Dependent Signaling Aberrations in Macronodular Adrenal Disease
Authors: BOURDEAU ISABELLE , STRATAKIS CONSTANTINE A.
Published: July 2009

Abstract: The adrenal glands are a major source of steroid hormone biosynthesis. In normal physiology, the pituitary hormone corticotropin (ACTH) regulates the secretion of glucocorticoids via its G protein‐coupled receptor (ACTHR), the product of the MC2R gene. Aldosterone is another major product of the adrenal gland; its regulation is controlled mainly by the renin‐angiotensin system, although ACTH plays a role, too, especially under certain pathological conditions. The adrenal gland also secretes lesser amounts of androgens and intermediate metabolites of all these steroids. Unregulated secretion of any of these hormones can be caused by tumors, adrenocortical adenomas or carcinomas, and/or bilateral (or, rarely, unilateral) hyperplasia. Cortisol‐producing hyperplasia of the adrenal glands is caused by two distinct syndromes, both of which have been directly or indirectly associated with protein kinase A signaling: (i) primary pigmented nodular adrenocortical disease (PPNAD) (a micronodular form of bilateral adrenal hyperplasia), either isolated (rarely) or in the context of Carney complex, is caused (in most cases) by mutations of the PRKAR1A gene; and (ii) ACTH‐independent macronodular adrenal hyperplasia (AIMAH), or massive macronodular adrenal disease (MMAD), has been associated with aberrant (ectopic) expression, and presumably regulation, of various G protein‐coupled receptors. AIMAH is a rare, sporadic condition affecting predominantly middle‐aged men and women with an almost equal ratio (the latter in contrast to other forms of endogenous Cushing's syndrome). Some familial cases of AIMAH have also been described, and it appears that the pathophysiological phenomena underlying AIMAH may be present in the far more common, sporadic adrenocortical tumors and, perhaps, in the nodular growth detected in the adrenal glands of the elderly in the general population. Thus, the study of ectopic receptor expression and cAMP‐dependent PKA activity in AIMAH may have wider implications for adrenal and, indeed, endocrine tumorigenesis.
Public Health Considerations in Human Consumption of Wild Game
Authors: AHL ALWYNELLE S. , NGANWA DAVID , WILSON SAUL
Published: July 2009

Abstract: The role of a few microorganisms, like Brucella and Mycobacterium and certain parasites of food animals, in causing human disease has been recognized for a hundred years. By the 1990s, other microorganisms derived from food animals were recognized as contributing to human illness. Handling and/or consumption of wild game may result in human exposure to novel microorganisms; these unrecognized or unknown agents or diseases in wild species may cross into humans and cause “new” diseases with which we are not familiar.
Goat Immune Response to Capripox Vaccine Expressing the Hemagglutinin Protein of Peste des Petits Ruminants
Authors: DIALLO A. , MINET C. , BERHE G. , LE GOFF C. , BLACK D. N. , FLEMING M. , BARRETT T. , GRILLET C. , LIBEAU G.
Published: July 2009

Abstract: Sheep‐pox and capripox are contagious diseases of domestic small ruminants for which the causal agent is a poxvirus classified into the Capripoxvirus genus. Viruses of this group have a host range specific to sheep, goats, cattle, and possibly buffalo. Thus, they are clearly indicated as vectors for the development of recombinant vaccines for peste des petits ruminants (PPR). Here we report the immune response of goats inoculated with a recombinant capripox‐PPR hemagglutinin.
Evaluation ofBrucella abortusStrain RB51 and Strain 19 in Pronghorn Antelope
Authors: ELZER PHILIP H. , SMITH J. , ROFFE T. , KREEGER T. , EDWARDS J. , DAVIS D.
Published: July 2009

Abstract:Free‐roaming elk and bison in the Greater Yellowstone Area remain the only wildlife reservoirs forBrucella abortusin the United States, and the large number of animals and a lack of holding facilities make it unreasonable to individually vaccinate each animal. Therefore, oral delivery is being proposed as a possible option to vaccinate these wild ungulates. One of the main problems associated with oral vaccination is the potential exposure of nontarget species to the vaccines. The purpose of this study was to determine the effects of twoBrucellavaccines, strain 19 (S19) and the rough strain RB51 (SRB51), in pregnant pronghorn antelope. We conclude that S19 and SRB51 rarely colonize maternal and fetal tissues of pregnant pronghorn and were not associated with fetal death. Oral delivery of either vaccine at this dose appears to be nonhazardous to pregnant pronghorn.
Use of the Mannan Receptor to Selectively Target Vaccine Antigens for Processing and Antigen Presentation through the MHC Class I and Class II Pathways
Authors: DAVIS W. C. , KONZEK R. L. , HAAS K. , ESTES D. M. , HAMILTON M. J. , CALL D. R. , APOSTOLOPOULOS V. , MCKENZIE I.F. C.
Published: July 2009

Abstract: Extensive studies have shown that synthetic and recombinant vaccines developed against hemoparasites have not been as effective as whole parasites or crude membrane fractions in eliciting protective immunity. A possible reason is that synthetic vaccines are not being presented in a form that induces the appropriate immune response. We have developed a bovine model system to evaluate the ability of adjuvant compounds to induce an immune response to peptide antigens dominated by a cytokine profile with a Type 1 (cell‐mediated) or Type 2 (humoral) bias. In the initial testing of this system, we found that mRNA expression of certain cytokines (interleukin [IL]‐1β, IL‐6, IL‐12, IL‐15, GM‐CSF, iNOS, and tumor necrosis factor [TNF]‐α) is enhanced when monocyte‐derived macrophages are stimulated with peptide antigen conjugated with mannan under oxidizing conditions compared to peptide conjugated with reduced mannan. The data suggest this model will be useful in identifying adjuvant systems that selectively modulate the cytokine profile of antigen presenting cells at the time of antigen presentation and the consequent downstream maturation of naive T cells to effector cells with Type 1 or Type 2 cytokine bias.
Age‐Related Innate Immune Response in Calves to Babesia bovis Involves IL‐12 Induction and IL‐10 Modulation
Authors: GOFF W. L. , JOHNSON W. C. , TUO W. , VALDEZ R. A. , PARISH S. M. , BARRINGTON G. M. , DAVIS W. C.
Published: July 2009

Abstract: There is a strong innate immunity in calves to infection with Babesia bovis. Interleukin (IL)‐12 and IL‐10 have been shown in vitro to be important immunoregulatory cytokines. Here we demonstrate in vivo that the protective innate response in young calves to infection with virulent B. bovis involves the early appearance of IL‐12 and interferon‐γ (IFN‐γ) transcripts in the spleen. In contrast, IL‐12 and IFN‐γ mRNA expression in the spleens of adult cattle that succumbed to the infection was delayed and depressed and occurred within the context of IL‐10 expression. Also in contrast with calves, there was no detectable antibody response before death in adults. A vigorous CD8+ T‐cell expansion occurred in the spleens of both calves and adults.
Use of Sentinel Herds to Study the Epidemiology of Vesicular Stomatitis in the State of Colorado
Authors: McCLUSKEY BRIAN J. , MUMFORD ELIZABETH L. , SALMAN MOWFAK D. , TRAUB‐DARGATZ JOSIE J.
Published: July 2009

Abstract:Approximately 20 sentinel premises in Colorado were visited quarterly during a 3‐year prospective study to investigate the persistence of VS viruses in horses. A survey to assess management practices, health events, animal movements and environmental data was completed at each visit. Collection of serum samples and oral swabs along with a clinical examination of sentinel horses were performed at each visit. Serum samples were tested by 2 or more of 4 available serological tests. The data collected for two years (August 1998 to August 2000) are reported here. During this period there was seroconversion in 1 and 8 horses based on capture IgM tests for seroytpes New Jersey and Indiana, respectively. Kaplan‐Meier curves were generated for those premises with horses that seroconverted and the mean survival time was 4.17 quarters (range 1.85‐7.0). The occurrence of seroconversions during periods when no clinical disease was observed suggests the persistence of vesicular stomatitis viruses in the environment of the sentinel premises.
Natural Aujeszky's Disease in a Spanish Wild Boar Population
Authors: GORTÁZAR C. , VICENTE J. , FIERRO Y. , LEÓN L. , CUBERO M. J. , GONZÁLEZ M.
Published: July 2009

Abstract: We describe an outbreak of Aujeszky's disease (AD) in a wild boar (Sus scrofa) population from central Spain. Mortality was estimated to be at least 14% (14/100) in juveniles and 7.5% (3/40) in adults. Most of the affected animals (12/17) were between 4 and 8 months of age. Gross lesions mainly consisted of enlarged and congestive tonsils and lymph nodes, petechial hemorrhages on the small intestine, and engorged blood vessels in the brain and meninges. Histopathology revealed mild nonsuppurative meningoencephalitis. Positivity to the fluorescent antibody test was found in tissues from the affected animals. Seroprevalence of antibodies to AD virus (ADV) was 56% (9/16). To our knowledge, this is the first description of clinical cases in a wild suid population.
Seroprevalence of Avian Paramyxovirus 1, 2, and 3 in Captive and Free‐Living Birds of Prey in Spain (Preliminary Results)
Authors: HÖFLE URSULA , BLANCO J. M. , KALETA E. F.
Published: July 2009

Abstract: Since December 1997, 700 blood plasma samples from 31 different species of captive and free‐living birds of prey from Spain were analyzed by hemagglutination inhibition (HI) test for the presence of antibodies to avian paramyxovirus (aPMV) 1,2, and 3. Out of 700 birds, 120 tested positive for aPMV‐1, 10 birds had antibodies to aPMV‐2, and 4 birds tested positive against aPMV‐3. Prevalence of antibodies against aPMV‐1 was significantly higher in captive than in free‐living birds of prey and in Falconiformes than in Strigidae and Accipitridae. Infection or exposure in captive birds may be due to the use of avian‐derived food in rehabilitation and captive‐breeding centers. This may be of concern at the time of reintroduction of these birds into free‐living populations.
Serologic Survey of Selected Viral, Bacterial, and Protozoal Agents in Captive and Free‐Ranging Ungulates from Central Kenya
Authors: KIMBER KEVIN R. , LUBROTH JUAN , DUBOVI EDWARD J. , BERNINGER MARY LOU , DEMAAR THOMAS W.
Published: July 2009

Abstract:Serologic evidence of exposure to various disease agents in free‐ranging and captive ungulates at a private game ranch in Kenya is presented, and seroprevalence values inside a fenced‐in area are compared with those found on the adjacent open savanna. Zebras outside the fence had a higher prevalence of equine rhinovirus‐1 than zebras inside (Fisher's exact test,P= 0.007); for all other species and all other agents, there was no such difference (P> 0.10). Results highlight possible transmission of these agents from domestic species into wildlife or vice versa at our study site.
The Hook Lake Wood Bison Recovery Project
Authors: NISHI J. S. , ELKIN B. T. , ELLSWORTH T. R.
Published: July 2009

Abstract: The Hook Lake Wood Bison Recovery Project (HLWBRP) is a wildlife conservation project aimed at recovering a captive, disease‐free herd of wood bison (Bison bison athabascae) from a wild herd infected with bovine tuberculosis (Mycobacterium bovis) and brucellosis (Brucella abortus). The disease eradication protocol that we have used involves a combination of techniques, including (1) orphaning of newborn wild‐caught calves to minimize exposure to B. abortus and M. bovis, (2) testing calves for maternal antibodies to brucellosis in the field prior to inclusion in the project, (3) isolating calves in pairs to prevent potential spread of disease, (4) prophylactic treatment using antimycobacterial and anti‐Brucella drugs, and (5) an intensive whole‐herd testing program for both diseases and removal of reactors. From 1996 to 1998, we captured a total of 62 calves; presently, 58 individuals comprise the founder herd. The captive‐born cohorts consist of 7 two‐year‐olds, 21 yearlings, and 22 calves. To date, there have been no cases of bovine tuberculosis or brucellosis in the captive herd.
Implications of Tuberculosis in African Wildlife and Livestock
Authors: MICHEL ANITA L.
Published: July 2009

Abstract:In most countries, tuberculosis caused byMycobacterium bovisis mainly a disease of domestic cattle and can be controlled successfully by means of a test‐and‐slaughter program. Once the infection spills over into a wild animal species with maintenance host potential, conventional measures are no longer sufficient to provide effective control. In South Africa, African buffaloes (Syncerus caffer) represent the most important maintenance host forM. bovis. Apart from transmitting the disease to predators and scavengers that feed on them, buffalo also serve as a source of infection to other wildlife species through environmental contamination. In several countries, it was shown that an infected wildlife reservoir that interacts with livestock causes frequent herd breakdowns and substantial economic losses to the agricultural sector. The outbreak of tuberculosis in free‐ranging wildlife populations thus poses a huge challenge on long‐term management and control strategies to prevent spillover into other wildlife, especially endangered, wildlife species and domestic livestock.
Bovine Tuberculosis in Michigan Wildlife and Livestock
Authors: SCHMITT STEPHEN M. , O'BRIEN DANIEL J. , BRUNING‐FANN COLLEEN S. , FITZGERALD SCOTT D.
Published: July 2009

Abstract: Since 1994, the state of Michigan has recognized a problem with bovine tuberculosis (TB), caused by Mycobacterium bovis, in wild white‐tailed deer from a 12‐county area in northeastern Lower Michigan. A total of 65,000 free‐ranging deer have been tested, and 340 have been found to be positive for M. bovis. The disease has been found in other wildlife species, and, in 1998, in domestic cattle, where to date 13 beef cattle and 2 dairy cattle herds have been diagnosed with bovine TB. Unfortunately, the situation is unique in that there have never been reports of self‐sustaining bovine TB in a wild, free‐ranging cervid population in North America. Scientists, biologists, epidemiologists, and veterinarians who have studied this situation have concluded that the most logical theory is that high deer densities and the focal concentration caused by baiting (the practice of hunting deer over feed) and feeding are the factors most likely responsible for the establishment of self‐sustaining TB in free‐ranging Michigan deer. Baiting and feeding have been banned since 1998 in counties where the disease has been found. In addition, the deer herd has been reduced by 50% in the endemic area with the use of unlimited antlerless permits. The measures of apparent TB prevalence have been decreased by half since 1997, providing hopeful preliminary evidence that eradication strategies are succeeding.
Buffalo‐Associated Theileria parva: The Risk to Cattle of Buffalo Translocation into the Highveld of Zimbabwe
Authors: LATIF A. A. , HOVE T. , KANHAI G. K. , MASAKA S.
Published: July 2009

Abstract: There has been an increase in the introduction of game animals, including African buffaloes, into the Highveld of Zimbabwe to establish private game reserves on condition that they are confined in separate and secured paddocks. Owing to shortages of pastures cattle were grazed in buffalo‐grazed paddocks resulting in outbreaks of buffalo‐derived theileriosis. This paper reports the results of epidemiological observations carried out on two game reserves to assess the risk of buffalo translocation. The infection rate with Theileria parasites in ticks collected from buffalo‐grazed pastures was high and produced fatal theileriosis in susceptible cattle. Similarly, adult R. appendiculatus ticks artificially fed as nymphs on the buffaloes produced fatal infections in susceptible cattle. Theileria parva (Boleni), the vaccine used to immunize cattle against theileriosis, and a buffalo‐derived T. parva stabilate (BV‐1) were inoculated in naïve buffaloes to study the Theileria carrier‐state in these animals. The two buffaloes that had received the Boleni stabilate showed no clinical theileriosis reaction; however, the ticks derived from them produced a subclinical reaction in one susceptible calf. The buffalo which had received stabilate BV‐1 developed fever, high schizont parasitosis for 10 days and 15% piroplasms parasitemia. R. appendiculatus ticks fed as nymphs on this buffalo produced fatal theileriosis reaction in a susceptible calf.
Ticks Associated with Armadillo (Euphractus sexcinctus) and Anteater (Myrmecophaga tridactyla) of Emas National Park, State of Goias, Brazil
Authors: BECHARA GERVÁSIO H. , SZABÓ M. P.J. , ALMEIDA FILHO W. V. , BECHARA J. N. , PEREIRA R. J.G. , GARCIA J. E. , PEREIRA MARCELO C.
Published: July 2009

Abstract:This study was conducted in October 1998 and November 1999 in the Emas National Park (131,868 ha), a savanna‐type cerrado region situated in the far south of Goias State, Brazil, near the geographic center of South America (15°‐23° S; 45°‐55° W). Animals were captured with the aid of nets and anesthetized (15 mg/kg ketamine + 1 mg/kg xylasine) in order to collect ticks for identification and to establish laboratory colonies. They included giant anteaters (Myrmecophaga tridactyla) (n= 4) and yellow armadillos (Euphractus sexcinctus) (n= 6). Free‐living ticks (larvae, nymphs, and adults) were collected from the field by using a 1 × 2‐m flannel cloth. Free‐living ticks were identified asAmblyommasp.,A. cajennense, andA. triste. Adult ticks collected from anteaters were identified asAmblyomma cajennenseandA. nodosumand from armadillos asA. pseudoconcolorandA. nodosum. The relevance of these host‐tick relationships to possible mechanisms underlying emergence of tick‐borne pathogens of importance to public health is discussed.
Adult Tick Burdens and Habitat Use of Sympatric Wild and Domestic Ungulates in a Mixed Ranch in Zimbabwe
Authors: DE GARINE‐WICHATITSKY M.
Published: July 2009

Abstract: Ticks do not usually infest sympatric hosts species according to their availability in a given environment, and it has been suggested that habitat use by hosts is a major determinant of tick burdens. The knowledge of such infestation patterns and their relationship with host habitat use is important for the control of the vectors of some major stock diseases in Africa, particularly in the context of mixed game/cattle ranching. In a ranch of Zimbabwe, we monitored the number of adult ticks found on cattle and wild ungulates. Tick burdens were measured weekly during one year on 12 heifers of an experimental herd (no acaricide used), and on wild ungulates occasionally shot for meat. Adult ticks were not evenly distributed among wild hosts, and infestation patterns corresponded to observations made by several authors in similar conditions. However, these infestation patterns could not be related to habitat use by ungulates, which had been previously monitored by road transect at the scale of the ranch, as these authors found a high niche overlap and no habitat segregation between ungulate species. In an attempt to relate habitat use by Brahman and Simmental heifers with the number of adult ticks collected during one day of grazing, we followed the heifers and recorded their position and activity (one or two days per week; each recording session was 7 h 30 min on average, for a total of 940 hours of survey). No correlation was found between the number of ticks collected and the distance (or time spent) traveled in each vegetation type or the number of grooming episodes. The possible role of other behavioral and physiological parameters is discussed, and the results are compared with those found for other tick‐host associations.
Epizootiology of Sixty‐Four Amphibian Morbidity and Mortality Events in the USA, 1996‐2001
Authors: GREEN D. EARL , CONVERSE KATHRYN A. , SCHRADER AUDRA K.
Published: July 2009

Abstract: A total of 44 amphibian mortality events and 20 morbidity events were reviewed retrospectively. The most common cause of amphibian mortality events was infection by ranaviruses (Family: Iridoviridae). Ranavirus epizootics have abrupt onset and affect late‐stage larvae and recent metamorphs. Mortality events due to ranavirus infections affected only widespread and abundant amphibian species, and there was a clear association with high population densities. Chytrid fungal infections accounted for seven mortality events in postmetamorphic anurans only. Chytrid epizootics are insidious and easily overlooked in the field. While both ranavirus and chytrid fungal epizootics were associated with > 90% mortality rates at affected sites, only the chytrid fungal infections were linked to multiple amphibian population declines. Three primitive fungal organisms in the newly erected clade, Mesomycetozoa, caused morbidities and mortalities in anurans and salamanders.
Intestinal Parasites Found in the Research Group of Mountain Gorillas in Bwindi Impenetrable National Park, Uganda
Authors: ROTHMAN JESSICA M. , BOWMAN DWIGHT D. , EBERHARD MARK L. , PELL ALICE N.
Published: July 2009

Abstract: Mountain gorillas (Gorilla gorilla beringei) are critically endangered, remaining only in two isolated populations in Central Africa. The objective of this study was to determine the prevalence and intensity of intestinal parasites in a single group of mountain gorillas in Bwindi Impenetrable National Park, Uganda over 7 weeks from June to August 2000. Fecal samples were collected from night nests and transported in formalin for examination at Cornell University and the Centers for Disease Control. All fecal samples were examined microscopically for parasitic larvae, cysts, and eggs. The following were found: strongylid eggs, Probstymaria sp. larvae, and two parasitic nematode larvae that were not identified. Additional examination techniques will be used to further examine the fecal material specifically for protozoan cysts. An increasing threat to this group of gorillas is the presence of local field assistants and researchers. We found no evidence of human parasites in the fecal samples from this gorilla group.
Causes of Mortality in the Florida Panther (Felis concolor coryi)
Authors: BUERGELT C. D. , HOMER B. L. , SPALDING M. G.
Published: July 2009

Abstract: Panthers necropsied at the University of Florida ranged between 2 weeks and 14 years of age; there were 38 males and 17 females in the cohort. Main categories of causes of death included trauma inflicted from either vehicular collisions (43%) or territorial fights (16%). Specific endogenous diseases involved the respiratory system in 13%, the urinary system in 4%, and the central nervous system in 2%. Ostium secundum atrial septal defects (ASD) were diagnosed in 11% of the panthers necropsied. Seventeen (54%) of the 38 male panthers had either unilateral or bilateral cryptorchidism. Cause of death remained undetermined in 11% of the total cohort.
Elk Restoration in Ontario, Canada
Authors: ROSATTE R. , HAMR J. , RANTA B. , YOUNG J. , COOL N.
Published: July 2009

Abstract:Ontario has embarked upon a program to restore elk (Cervus elaphus) that were once native to that province. A comprehensive disease‐management strategy has ensured that elk are free of infectious diseases such as brucellosis and tuberculosis prior to shipment to Ontario. Postmortem analysis occurs on elk mortalities in Ontario to ensure that elk are not infected with diseases such as chronic wasting disease and tuberculosis. Between 1998 and 2001, a total of 443 elk were transported from Elk Island National Park, Alberta, and released in four different areas of Ontario. Cumulative mortality for elk in all areas was 26% from 1998 to January 2001. The primary causes of mortality were post‐release stress‐induced emaciation (21%), wolf predation (20%), transport/handling injuries (10%), bacterial infections (10%), and drowning (7%). Female calves had the highest mortality rates (37%) compared to the other sex and age cohorts (23‐24%). Preliminary findings suggest an inverse correlation between the length of time elk are held in enclosures prior to release and the distance they disperse from the release site. The 2001 estimated population of elk in Ontario is about 400 individuals.
Pheochromocytoma
Authors: BRAVO EMMANUEL L.
Published: July 2009

Abstract:Pheochromocytoma and paragangliomas are rare tumors of chromaffin tissue that secrete catecholamines either intermittently or continuously, producing hypertension with a constellation of symptoms and signs that can be frightening to the patient and that continue to provide perplexing problems for clinicians. With surgical treatment, symptoms will be relieved and hypertension normalized or ameliorated for patients who do not have malignant tumors. Appropriate antihypertensive drugs are used to manage hypertension, to control associated cardiovascular symptoms, and to prepare patients for operation. The question debated most often regarding medical therapy of pheochromocytoma is whether antihypertensive treatment regimens other than nonspecific alpha‐blockade are just as effective and safe. Understanding the pathophysiologic mechanisms that sustain the hypertension and the pharmacology of antihypertensive agents allows better selection of antihypertensive therapy.
New Therapeutic and Surgical Approaches for Sporadic and Hereditary Pheochromocytoma
Authors: WALTHER McCLELLAN M.
Published: July 2009

Abstract:Pheochromocytoma is a rare, surgically correctable cause of hypertension. Modern medical blockade has significantly improved patient survival and morbidity. The last decade has seen the identification of the genes responsible for several hereditary causes of pheochromocytoma. Evaluation of these patients has demonstrated different catecholamine profiles associated with the different syndromes. Genetic testing and new, more sensitive catecholamine tests are allowing better, earlier diagnosis of affected patients. Some patients with small tumors deemed nonfunctional by traditional methods may be safely observed until function is demonstrated. Laparoscopic surgery has supplanted the use of open surgery in the management of these tumors. Adrenocortical‐sparing surgery may be performed using laparoscopy in patients with hereditary forms of pheochromocytoma.
The Pathophysiology of Aldosterone in the Cardiovascular System
Authors: ROCHA RICARDO , FUNDER JOHN W.
Published: July 2009

Abstract: Until relatively recently, the mineralocorticoid hormone aldosterone was thought to be produced uniquely in the adrenal cortex and to act exclusively on epithelia to promote sodium retention and potassium excretion. However, it is now known that aldosterone also acts on nonepithelial tissues, such as brain, heart, and blood vessels, and that enzymes required for aldosterone biosynthesis are expressed in these same tissues, which may be consistent with local aldosterone production acting in a paracrine fashion. A number of studies indicate that aldosterone exerts clearly deleterious effects when levels are inappropriate for salt status. For example, aldosterone in a high‐salt environment initiates a vascular inflammation response that leads to cardiac and vascular pathologies. In experimental models of hypertension and heart failure, the nonepithelial effects of aldosterone are mediated via classical mineralocorticoid receptors, and are largely or completely abolished by administration of the selective aldosterone blocker eplerenone or by reduction of circulating aldosterone by adrenalectomy. In the present manuscript, we review some of the most recent discoveries in the field of aldosterone biology, with special emphasis on the mechanisms involved in the deleterious actions of this mineralocorticoid in cardiovascular tissues.
The Role of PET in Localization of Neuroendocrine and Adrenocortical Tumors
Authors: ERIKSSON BARBRO , BERGSTRÖM MATS , SUNDIN ANDERS , JUHLIN CLAES , ÖRLEFORS HÅKAN , ÖBERG KJELL , LÅNGSTRÖM BENGT
Published: July 2009

Abstract: Positron emission tomography (PET) supplies a range of labeled compounds to be used for the characterization of tumor biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow up, and clinical research. The first routinely used PET tracer in oncology, 18F‐labeled deoxyglucose (FDG), was successfully used for diagnosis of cancer, reflecting increased expression of glucose transporter in cancerous tissue. This tracer, however, usually does not show sufficient uptake in well‐differentiated tumors such as neuroendocrine tumors. We developed a tracer more specific to neuroendocrine tumors—the serotonin precursor 5‐hydroxytryptophan (5‐HTP) labeled with 11C—and demonstrated increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was so selective and the resolution was so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. To further improve the method, especially to reduce the high renal excretion of the tracer producing streaky artifacts in the area of interest, we introduced premedication by the decarboxylase inhibitor carbidopa, leading to a six‐fold decreased renal excretion while the tumor uptake increased three‐fold, hence improving the visualization of the tumors.

11C‐labeled l‐DOPA was evaluated as an alternative tracer, especially for endocrine pancreatic tumors, which usually do not demonstrate enhanced urinary serotonin metabolites. However, only half of the EPTs, mainly functioning tumors, could be detected with l‐DOPA. Instead 5‐HTP seems to be a universal tracer for EPT and foregut carcinoids. With new, more sensitive PET cameras, larger field of view and procedures for whole‐body coverage, the PET examination with 5‐HTP is now routinely performed as reduced whole‐body PET examinations with coverage of the thorax and abdomen. With this method we have been able to visualize small neuroendocrine lesions in the pancreas and thorax (e.g., ACTH‐producing bronchial carcinoids) not detectable by any other method, including octreotide scintigraphy, MRI, and CT. Another tracer, the 11β‐hydroxylase inhibitor, metomidate labeled with 11C, was developed to simplify diagnosis and follow‐up of patients with incidentalomas. A large series of patients with incidentally found adrenal masses have been investigated and so far all lesions of adrenocortical origin have been easily identified because of exceedingly high uptake of 11C‐metomidate, whereas noncortical lesions showed very low uptake. In addition, adrenocortical cancer shows high uptake, suggesting that this PET tracer can be used for staging purposes.
Effects of Short‐ and Long‐Term Nicotine Treatment on Intracellular Calcium and Tyrosine Hydroxylase Gene Expression
Authors: SABBAN ESTHER L. , GUEORGUIEV VOLODIA D.
Published: July 2009

Abstract:It is important to determine how the signaling pathways for the short‐term effects of nicotine (catecholamine secretion, phosphorylation of tyrosine hydroxylase) differ from those required for changes in gene expression. Our aim was to distinguish the pathways involved in short‐ and long‐term nicotinic stimulation. PC12 cells were treated with several concentrations of nicotine from 10 μM to 1 mM. All elicited a rapid and transient rise in [Ca2+]i, which was concentration dependent. After several minutes of continued exposure, a second smaller sustained rise in [Ca2+]iwas only observed with intermediate concentrations of nicotine (50‐200 μM). This sustained rise was not observed in cells pretreated with α‐bungarotoxin (α‐BTX). α‐BTX also prevented the elevation of tyrosine hydroxylase mRNA by nicotine. The effects of brief and prolonged treatment with nicotine on the signaling pathways involved in changes in [Ca2+]iand induction of tyrosine hydroxylase gene expression are summarized. The results indicate that nicotine may elicit different signaling pathways depending on the concentration. The sustained elevation of [Ca2+]ivia activation of α7 nAChRs is proposed as the mechanism leading to increased tyrosine hydroxylase gene expression.
Location, Development, Control, and Function of Extraadrenal Phenylethanolamine N‐Methyltransferase
Authors: ZIEGLER MICHAEL G. , BAO XUPING , KENNEDY BRIAN P. , JOYNER ALEX , ENNS ROBERT
Published: July 2009

Abstract: Phenylethanolamine N‐methyltransferase (PNMT) methylates norepinephrine (NE) to form epinephrine (E). It is present in a high concentration in the adrenal medula but occurs in many other tissues throughout the body. In the brain stem and retina PNMT is present in specific neurons. Cardiac PNMT develops early in the fetal heart and is found in relatively high levels in the adult left atrium. Intrinsic cardiac adrenergic cells are distributed throughout the adult myocardium and contain all the enzymes necessary for E synthesis. The PNMT gene promoter region contains a glucocorticoid response element; however, the initial development of brain and cardiac fetal PNMT is glucocorticoid independent. Rat fetal heart PNMT peaks at embryonic day 11 and becomes sensitive to glucocorticoid induction by day 12. PNMT‐containing cells are concentrated in the atrioventricular canal and interventricular septum during cardiac development, areas important in the development of the cardiac conduction system. In the adult rat, cardiac PNMT is inducible by glucocorticoids and synthesizes E. Glucocorticoids are essential for development of the high levels of PNMT in the adrenal, but are less important outside the adrenal. The PNMT gene contains 3 exons and 2 introns. Adrenal PNMT mRNA exists as a single type, but in the heart PNMT mRNA is present as both an intronless and an intron‐containing type. In some cardiac tissues, glucocorticoids decrease levels of intron‐containing PNMT mRNA and increase intronless PNMT mRNA and PNMT activity. Studies in adrenalectomized animals suggest that extraadrenal PNMT increases blood pressure, blood glucose, and lymphocyte cytokine production. PNMT may also play a role in the regulation of fetal heart rate prior to development of the adrenal medulla.
Functional Nicotinic Acetylcholine Receptor Expression on Stem and Progenitor Cells of the Early Embryonic Nervous System
Authors: SCHNEIDER A. S. , ATLURI P. , SHEN Q. , BARNES W. , MAH S. J. , STADFELT D. , GODERIE S. K. , TEMPLE S. , FLECK M. W.
Published: July 2009

Abstract:Although the adult brain contains nicotinic acetylcholine (ACh) receptors vital to cortical function, little is known about the assembly of embryonic receptor subunits into functional receptors or their role in fetal brain development. We now report the first evidence of functional nicotinic ACh receptors on stem and progenitor cells of fetal mouse cerebral cortex as early as embryonic day 10.
Serum Deprivation‐Induced Upregulation of Voltage‐Dependent Sodium Channels in Adrenal Chromaffin Cells
Authors: YANAGITA TOSHIHIKO , KOBAYASHI HIDEYUKI , YOKOO HIROKI , SAITOH TOMOKAZU , MINAMI SHIN‐ICHI , SHIRAISHI SEIJI , UEZONO YASUHITO , WADA AKIHIKO
Published: July 2009

Abstract: In the present study, we investigated whether activation of the MAPK family could regulate the cell surface expression of Na channels in cultured bovine adrenal chromaffin cells. The results suggest that constitutively activated ERK (but not p38 or JNK), by various extracellular stimuli, downmodulates the density of cell surface Na channels, which was mediated via the destabilization of Na channel α‐subunit mRNA.
Role of CAPS in Dense‐Core Vesicle Exocytosis
Authors: WASSENBERG JAMES J. , MARTIN THOMAS F.J.
Published: July 2009

Abstract: Calcium‐dependent activator protein for secretion (CAPS) was initially identified in brain cytosol based on its ability to reconstitute calcium‐triggered dense‐core vesicle (DCV) exocytosis in permeable cell lines (PC12) of adrenal chromaffin origin. Current evidence indicates that CAPS functions selectively in DCV exocytosis by interacting with DCVs, the plasma membrane, and protein components of the fusion machinery. To further delineate the role of CAPS in endocrine and neural secretion, the tissue distribution of CAPS was determined. Immunoreactive CAPS I localized exclusively to neural and endocrine tissues including adrenal medulla, pancreatic islets, anterior pituitary, thyroid parafollicular C cells, gastrointestinal G cells, renal juxtaglomerular cells, and gray matter throughout the central nervous system. The results are consistent with a widespread functional role of CAPS in the regulated exocytosis of DCVs in the nervous and endocrine systems.
Separating Vesicle Fusion and Exocytosis in Hypertonic Conditions
Authors: TROYER KEVIN P. , MUNDORF MICHELLE L. , FRIES HARVEY E. , WIGHTMAN R. MARK
Published: July 2009

Abstract: The existence of an osmotic gradient between the vesicular contents of chromaffin and mast cells and the extracellular fluid plays a key role in the exocytotic process. Altering this gradient by elevating the external buffer osmolarity allows for the inhibition of exocytosis from cells and isolation and identification of prespike current events upon stimulation using cyclic voltammetry. Subsequent replacement of the osmotic gradient leads to release of the contents from fused vesicles.
Genomic and Physiological Analysis of Oxygen Sensitivity and Hypoxia Tolerance in PC12 Cells
Authors: SETA KAREN , KIM HIE‐WON , FERGUSON TSUNEO , KIM RICHARD , PATHROSE PETERSON , YUAN YONG , LU GANG , SPICER ZACHARY , MILLHORN DAVID E.
Published: July 2009

Abstract: The mechanisms by which cells adapt and respond to changes in oxygen tension remain largely unknown. Our laboratory has used the PC12 cell line to study both biophysical and molecular responses to hypoxia. This chapter summarizes our findings. We found that membrane depolarization that occurred when PC12 cells were exposed to reduced O2 was mediated by a specific potassium channel, the Kv1.2 channel. The membrane depolarization leads to increased Ca2+ conductance through a voltage‐sensitive channel, which in turn mediates the release of the neurotransmitters dopamine, adenosine, glutamate, and GABA. In addition, increased intracellular Ca2+ and other signaling systems regulate hypoxia‐induced gene expression, which contributes to the adaptive response to reduced O2+. We identified several critical signaling pathways that regulate a complex gene expression profile in PC12 cells during hypoxia. These include the cAMP‐protein kinase A, Ca2+‐calmodulin, p42/44 mitogen‐activated protein kinase (MAPK), stress‐activated protein kinase (SAPK; p38 kinase), and the phosphatidylinositol 3‐kinase‐AKT as regulators of gene expression. Several of these pathways regulate hypoxia‐specific transcription factors that are members of the hypoxia‐inducible factor (HIF) family. Recently, we have successfully used subtractive cDNA libraries and microarray analysis to identify the genomic profile that mediates the cellular response to hypoxia.
Expression and Functional Characterization of the Serine Protease Inhibitor Neuroserpin in Endocrine Cells
Authors: HILL RENA M. , COATES LEIGH C. , PARMAR PARMJEET K. , MEZEY EVA , PEARSON JOHN F. , BIRCH NIGEL P.
Published: July 2009

Abstract: Serine proteases play essential roles in a wide variety of cellular processes in endocrine cells. There is a growing interest in the roles of serine protease inhibitors, or serpins, as key regulators of their activity. We have cloned two neuroserpin cDNAs from a rat pituitary cDNA library and confirmed tissue plasminogen activator as a potential target for this inhibitor. We show that neuroserpin transcripts are expressed by endocrine cells in the adrenal and pituitary glands and that immunoreactive neuroserpin is stored in densely cored secretory granules in these cells. Overexpression of neuroserpin in an anterior pituitary corticotroph cell line results in the extension of neurite‐like processes, suggesting that neuroserpin may play a role in cell communication, cell adhesion, and/or cell migration.
The Local Chromaffin Cell Plasminogen/Plasmin System and the Regulation of Catecholamine Secretion
Authors: JIANG QIJIAO , YASOTHORNSRIKUL SUKKID , TAUPENOT LAURENT , MILES LINDSEY A. , PARMER ROBERT J.
Published: July 2009

Abstract: Chromaffin cells express components of the plasminogen/plasmin system, including its major activator, tissue plasminogen activator (t‐PA), and high‐affinity cellular receptors for plasminogen, which promote local concentration and activation of plasminogen at the cell surface. Our studies suggest that plasmin participates in local neuroendocrine prohormone processing and that perturbation of this system profoundly affects the secretory characteristics of the cells. These results suggest the presence of a local, functionally active, chromaffin cell plasminogen/plasmin system that plays a major role in the regulation of catecholamine release from catecholaminergic cells.
Composition of the Heme Centers in Chromaffin Granule Cytochrome b561
Authors: KAMENSKY YURY , KULMACZ RICHARD J. , PALMER GRAHAM
Published: July 2009

Abstract: Electron paramagnetic resonance and circular dichroism spectra of cytochrome b561 from chromaffin granule membranes indicated a 2:1 stoichiometry of high‐ and low‐potential hemes. Recombinant bovine cytochrome b561 expressed in a baculovirus system retained native spectroscopic characteristics and represents a promising model for further study.
From the Neural Crest to Chromaffin Cells
Authors: KALCHEIM CHAYA , LANGLEY KEITH , UNSICKER KLAUS
Published: July 2009

Abstract: The autonomic nervous system consists of sympathetic, parasympathetic, and enteric ganglia and also of a specialized neuroendocrine derivative, the adrenomedullary chromaffin cells.
Gene Targeting Reveals Multiple Essential Functions of the Neuregulin Signaling System during Development of the Neuroendocrine and Nervous Systems
Authors: CRONE STEVEN A. , LEE KUO‐FEN
Published: July 2009

Abstract: Mice harboring targeted mutations in neuregulin‐1 and its receptors (erbB2, erbB3, and erbB4) have been invaluable tools for testing the roles of these genes in vivo as well as for identifying unexpected functions for this signaling system. This review summarizes the advances in understanding the myriad functions of neuregulins in the nervous and neuroendocrine systems that have been revealed by examining gene‐targeted mice.