Testes function, feedlot performance, and carcass traits were evaluated in bulls actively immunized against gonadotropin-releasing hormone (GnRH) at different ages. Bull calves were randomly assigned ...to one of seven treatment groups (n = 15 calves/group). Calves were unimmunized (Group 1), immunized at 1.5, 4, 7, or 12 mo of age with a GnRH-keyhole limpet hemocyanin (KLH) conjugate (Groups 2 to 5, respectively), or castrated at 4 mo of age (Groups 6 and 7). Immunized bulls did not receive a secondary, or booster, immunization. Calves in group 6 received Synovex-C at castration and Synovex-S at weaning and feedlot entry. Anti-GnRH titer was evident at slaughter in all immunized bulls. However, the final immune response of bulls immunized at 1.5 mo was significantly lower than the response of bulls immunized at later stages of development. Final scrotal circumference and testis weight in bulls immunized at 4, 7, or 12 mo of age were significantly reduced relative to unimmunized bulls. The final live weight, feedlot gain, and carcass weight of immunized and unimmunized bulls did not differ (P 0.05) from the same parameters in steers implanted with Synovex. Longissimus muscle area, marbling score, and backfat thickness did not differ between immunized and unimmunized bulls. The sex class score of the carcasses of immunized bulls did not differ from the score of steer carcasses. In contrast, a significantly higher proportion of carcasses from unimmunized bulls graded as bullock carcasses. Taken together, these data indicate that a single immunization against GnRH at 4 to 12 mo of age results in significant attenuation of testicular growth in bulls. These data also demonstrate that immunization against GnRH reduces the masculinity of carcasses from bulls, but does not affect feedlot performance, longissimus muscle area, marbling score, or backfat thickness. These results suggest that single immunization with the GnRH-KLH conjugate may have practical utility as a noninvas
A North Dakota strain of the Colorado potato beetle,
Leptinotarsa decemlineata (Say), was reared under both short- (8L:16D) and long-day (17L:7D) conditions. Age-related and pyriproxyfen- (JHA-) ...induced changes in hemolymph free amino acids and proteins were examined. Under a short-day photoperiod, the total free amino acid concentration in the hemolymph increased gradually up to 20 days of adult life, but the long-day beetles showed marked increases during the first 10 days and then decreased afterwards. Proline, glutamine and valine were the most abundant free amino acids in both sexes of beetles held under either short- or long-day photoregims. JHA treatment of diapausing adults, held under either short- or long-day conditions after treatment, terminated diapause as indicated by re-emergence from the vermiculite, feeding, mating, changes in free amino acid levels, the disappearance of diapause protein 1 and appearance of vitellogenin in the hemolymph. Furthermore, most of the JHA-treated females held under long-day conditions also matured oocytes and oviposited, but those held under short-day conditions did not.
Objective: To report the functional imaging experience with a 29-year-old woman carrying a mutation in the fumarate hydratase (FH)-encoding gene and a history of a pheochromocytoma (PHEO) and ...retroperitoneal paraganglioma (PGL).Methods: The patient was found to have a splice-site mutation in the FH gene at intron 2, c.268-2A>G. To confirm this, immunohistochemical staining was performed on tumor tissue slides from the patient's previous surgeries. The patient underwent biochemical testing for PHEO/PGL, which included chromogranin A and plasma methoxytyramine. The patient's tumors were also imaged using several imaging modalities, including computed tomography (CT), magnetic resonance imaging, ultrasound, and positron emission tomography (PET)/CT studies using 18F-fluorodeoxyglucose (18F-FDG), 18F-fluorodopamine (18F-FDA), 18F-fluorodihydroxyphenylalanine (18F-FDOPA), and 68Ga-tetraazacyclododecanetetraacetic acid–Tyr3-octreotate (68Ga-DOTATATE) as tracers.Results: The patient received a comprehensive evaluation based on her symptoms and medical history. She was found to have 3 noradrenergic-secreting tumors that showed uptake on 18F-FDG-(2/3), 68Ga-DOTATATE-(2/3), 18F-FDOPA-(3/3), and 18F-FDA-(3/3) PET/CT. The patient was recommended to have the tumor sites removed (renal hilum, aortocaval, and periaortic regions) with lympadenectomies to address possible metastases. Pathology confirmed paraganglioma. Immunohistochemical staining from previous surgical slides showed negative staining for FH, consistent with a mutation in the gene.Conclusion: We share, for the first time, functional images for an FH mutation–positive PHEO/PGL patient using various PET radiopharmaceuticals. 18F-FDA- and 18F-FDOPA PET/CT served as the best imaging modalities. This case provides the appropriate selection of imaging studies and further evidence for the importance of screening for FH mutations in patients with noradrenergic PHEOs/PGLs.Abbreviations: CT = computed tomography 18F-FDA = 18F-fluorodopamine 18F-FDG = 18F-fluorodeoxyglucose 18F-FDOPA = 18F-fluorodihydroxyphenylalanine FH = fumarate hydratase 68Ga-DOTATATE = 68Ga-tetraazacyclododecanetetraacetic acid–Tyr3-octreotate MTY = methoxytyramine NIH = National Institutes of Health PET = positron emission tomography PGL = paraganglioma PHEO = pheochromocytoma SDHB = succinate dehydrogenase complex, subunit B URL = upper reference limit
Individuals with obsessive-compulsive disorder often identify psychosocial stress as a factor that exacerbates their symptoms, and many trace the onset of symptoms to a stressful period of life or a ...discrete traumatic incident. However, the pathophysiological relationship between stress and obsessive-compulsive disorder remains poorly characterized: it is unclear whether trauma or stress is an independent cause of obsessive-compulsive disorder symptoms, a triggering factor that interacts with a preexisting diathesis, or simply a nonspecific factor that can exacerbate obsessive-compulsive disorder along with other aspects of psychiatric symptomatology. Nonetheless, preclinical research has demonstrated that stress has conspicuous effects on corticostriatal and limbic circuitry. Specifically, stress can lead to neuronal atrophy in frontal cortices (particularly the medial prefrontal cortex), the dorsomedial striatum (caudate), and the hippocampus. Stress can also result in neuronal hypertrophy in the dorsolateral striatum (putamen) and amygdala. These neurobiological effects mirror reported neural abnormalities in obsessive-compulsive disorder and may contribute to an imbalance between goal-directed and habitual behavior, an imbalance that is implicated in the pathogenesis and expression of obsessive-compulsive disorder symptomatology. The modulation of corticostriatal and limbic circuits by stress and the resultant imbalance between habit and goal-directed learning and behavior offers a framework for investigating how stress may exacerbate or trigger obsessive-compulsive disorder symptomatology.
Aims
Contrasting findings exist regarding the association between circulating sex hormone-binding globulin (SHBG) and testosterone levels and type 2 diabetes (T2D) in men. We examined prospective ...associations of SHBG and sex steroids with incident T2D in a cohort of community-dwelling men.
Methods
Participants were from a cohort study of community-dwelling (
n
= 2563), middle-aged to elderly men (35–80 years) from Adelaide, Australia (the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study). The current study included men who were followed for 5 years and with complete SHBG and sex steroid levels (total testosterone (TT), dihydrotestosterone (DHT) and oestradiol (E2)), but without T2D at baseline (
n
= 1597). T2D was identified by either self-report, fasting glucose (≥ 7.0 mmol/L), HbA1c (≥ 6.5%/48.0 mmol/mol), and/or prescriptions for diabetes medications. Logistic binomial regression was used to assess associations between SHBG, sex steroids and incident T2D, adjusting for confounders including age, smoking status, physical activity, adiposity, glucose, triglycerides, symptomatic depression, SHBG and sex steroid levels.
Results
During an average follow-up of 4.95 years, 14.5% (
n
= 232) of men developed new T2D. Multi-adjusted models revealed an inverse association between baseline SHBG, TT, and DHT levels, and incident T2D (odds ratio (OR) = 0.77, 95% CI 0.62, 0.95,
p
= 0.02; OR 0.70 0.57, 0.85,
p
< 0.001 and OR 0.78 0.63, 0.96,
p
= 0.02), respectively. However, SHBG was no longer associated with incident T2D after additional adjustment for TT (OR 0.92 0.71, 1.17,
p
= 0.48; TT in incident T2D: OR 0.73 0.57, 0.92,
p
= 0.01) and after separate adjustment for DHT (OR 0.83 0.64, 1.08,
p
= 0.16; DHT in incident T2D: OR 0.83 0.65, 1.05,
p
= 0.13). There was no observed effect of E2 in all models of incident T2D.
Conclusions
In men, low TT, but not SHBG and other sex steroids, best predicts the development of T2D after adjustment for confounders.
The immune suppression that characterizes human helminth infections can hinder the development of protective immunity or help to reduce pathogenic inflammation. Signaling through the T cell ...costimulator glucocorticoid-induced TNFR-related protein (GITR) counteracts immune downregulation by augmenting effector T cell responses and abrogating suppression by Foxp3(+) regulatory T cells. Thus, superphysiological Ab-mediated GITR costimulation represents a novel therapy for promoting protective immunity toward parasitic helminths, whereas blocking physiological GITR-GITR ligand (GITRL) interactions may provide a mechanism for dampening pathogenic Th2 inflammation. We investigated the superphysiological and physiological roles of the GITR-GITRL pathway in the development of protective and pathogenic Th2 responses in murine infection models of filariasis (Litomosoides sigmodontis) and schistosomiasis (Schistosoma mansoni). Providing superphysiological GITR costimulation using an agonistic anti-GITR mAb over the first 12 d of L. sigmodontis infection initially increased the quantity of Th2 cells, as well as their ability to produce Th2 cytokines. However, as infection progressed, the Th2 responses reverted to normal infection levels, and parasite killing remained unaffected. Despite the Th2-promoting role of superphysiological GITR costimulation, Ab-mediated blockade of the GITR-GITRL pathway did not affect Th2 cell priming or maintenance during L. sigmodontis infection. Blockade of GITR-GITRL interactions during the acute egg phase of S. mansoni infection resulted in reduced Th2 responses, but this effect was confined to the spleen and did not lead to changes in liver pathology. Thus, although superphysiological GITR costimulation can therapeutically enhance Th2 responses, physiological GITR-GITRL interactions are not required for the development of Th2-mediated resistance or pathology in murine models of filariasis and schistosomiasis.
Relationships between tree traits and tree value for lumber production were investigated. For the purposes of estimating relative economic weights for use in multitrait selection in coastal ...Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii), tree height, diameter at breast height, and branch diameter were measured on 164 trees (ages 36-66 years). Increment cores from a subsample (92) of these trees were assayed by X-ray densitometry to determine wood density. Bole volume was derived by summing the log volumes of all logs from each tree. Value of lumber recovered from each tree was determined in a separate mill study using both visual and machine stress rated (MSR) grading rules. Multiple linear regression was used to relate tree value to the growth and wood quality traits. Stem volume and branch diameter significantly influenced tree value under visual grading, with relative economic weights of 0.06 dm3 and -5.22 cm, respectively. Wood density significantly influenced tree value under MSR grading (relative economic weights: 0.06 dm3, -6.69 cm, and 0.06 kg/m3, respectively), where lumber strength is measured more accurately. These regression coefficients can be used directly as economic weights in selection indices.
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