Clinical evaluations of pituitary apoplexy in incidental nonfunctional pituitary adenomas

Pituitary apoplexy is an uncommon syndrome that often results in spontaneous hemorrhage or infarction of pituitary tumors or glands. We previously reported pituitary apoplexy occurred most frequently in nonfunctional pituitary adenomas among all types of pituitary incidentalomas. In the present study, we aimed to investigate the characteristics of pituitary apoplexy in patients with incidental nonfunctional pituitary adenomas. 65 patients with pituitary incidentaloma were enrolled. All patients underwent clinical/endocrinological/pathological investigations. As a result, 33 patients were diagnosed with nonfunctional pituitary adenomas. Of these, 12.1% of patients had pituitary apoplexy. There was no difference in tumor diameter, age, or sex between the apoplexy and the non-apoplexy groups. However, the liver enzymes aspartate transaminase and alanine aminotransferase were significantly higher, and plasma sodium and chloride levels were significantly lower in the apoplexy group than in the non-apoplexy group (each P < .05). In addition, low-density lipoprotein-cholesterol was significantly higher in the apoplexy group than in the non-apoplexy group (P < .05). Besides, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin deficiencies were significantly more frequent in the apoplexy group than in the non-apoplexy group (each P < .05), and growth hormone and adrenocorticotropic hormone deficiencies were more frequent in the apoplexy group than in the non-apoplexy group (P = .09 and.08, respectively). Furthermore, tumor diameter was not associated with pituitary apoplexy, whereas thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone deficiencies were significantly associated with the apoplexy group (each P < .05). Hence, the present study indicated that pituitary apoplexy could not be related to tumor diameter. Moreover, hormonal deficiencies, hepatic dysfunction, hyponatremia or hypochloremia, and dyslipidemia might be indicators of pituitary apoplexy. There could be the possibility the treatment for dyslipidemia prevents pituitary apoplexy.     

Prolyl Isomerase Pin1 Expression in the Spinal Motor Neurons of Patients With Sporadic Amyotrophic Lateral Sclerosis

Background and PurposeAmyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Selective deficiency of edited adenosine deaminase acting on RNA 2 (ADAR2), a key molecule in the acquisition of Ca²⁺ resistance in motor neurons, has been reported in sporadic ALS (sALS) spinal motor neurons. Since ADAR2 activity is positively regulated by prolyl isomerase Protein never in mitosis gene A interacting-1 (Pin1), a known phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, we investigated Pin1 expression in spinal motor neurons in sALS.MethodsSpecimens of the spinal cord were obtained from the lumbar region in eight sALS patients and age-matched five controls after postmortem examinations. The specimens were double stained with anti-Pin1 and anti-TAR DNA-binding protein of 43 kDa (TDP-43) antibodies, and examined under a fluorescence microscope.ResultsThis study analyzed 254 and 422 spinal motor neurons from 8 sALS patients and 5 control subjects, respectively. The frequency of motor neurons with high cytoplasmic Pin1 expression from the spinal cord did not differ significantly between sALS specimens without cytoplasmic TDP-43 inclusions and control specimens. However, in sALS specimens, neurons for which the Pin1 immunoluminescence intensity in the cytoplasm was at least twice that in the background were more common in specimens with cytoplasmic TDP-43 inclusions (p<0.05 in χ² test).ConclusionsIn sALS, neurons with higher expression levels of Pin1 levels had more TDP-43 inclusions. Despite the feedback mechanism between Pin1 and ADAR2 being unclear, since Pin1 positively regulates ADAR2, our results suggest that higher Pin1 expression levels in motor neurons with TDP-43 pathology from sALS patients represent a compensatory mechanism.     

Methodological extensions of meta-analysis with excess relative risk estimates: application to risk of second malignant neoplasms among childhood cancer survivors treated with radiotherapy

Although radiotherapy is recognized as an established risk factor for second malignant neoplasms (SMNs), the dose response of SMNs following radiotherapy has not been well characterized. In our previous meta-analysis of the risks of SMNs occurring among children who have received radiotherapy, the small number of eligible studies precluded a detailed evaluation. Therefore, to increase the number of eligible studies, we developed a method of calculating excess relative risk (ERR) per Gy estimates from studies for which the relative risk estimates for several dose categories were available. Comparing the calculated ERR with that described in several original papers validated the proposed method. This enabled us to increase the number of studies, which we used to conduct a meta-analysis. The overall ERR per Gy estimate of radiotherapy over 26 relevant studies was 0.60 (95%CI: 0.30–1.20), which is smaller than the corresponding estimate for atomic bomb survivors exposed to radiation as young children (1.7; 95% CI: 1.1–2.5). A significant decrease in ERR per Gy with increase in age at exposure (0.85 times per annual increase) was observed in the meta-regression. Heterogeneity was suggested by Cochran''s Q statistic (P < 0.001), which may be partly accounted for by age at exposure.     

Effectiveness of steroid therapy for pancreatic cysts complicating autoimmune pancreatitis and management strategy for cyst-related complications

Abstract

Objectives: Autoimmune pancreatitis (AIP) sometimes becomes complicated with pancreatic cysts, although their detailed characteristics and management strategy have not been fully determined. We aimed to clarify the efficiency of steroid therapy and the risk factors for cyst formation and cyst-related complications.

Methods: One hundred sixty-three AIP patients were retrospectively analyzed for relevant factors of cyst formation. We compared subjects with and without steroids to evaluate drug effectiveness on cyst size change and investigated the factors associated with cyst-related complications.

Results: Thirty-two patients (19.6%) had complicating pancreatic cyst formation, and 40 cystic lesions of ≥10?mm in size were detected. Multivariate analysis revealed a drinking habit, abdominal/back pain, and elevated serum amylase to be significantly associated with cyst formation. Steroid-treated cysts became significantly reduced in size in the short-term and disappeared significantly more frequently within 1-year as compared with non-treated ones, which was confirmed by multivariate analysis. Six of 40 cysts exhibited cyst-related complications significantly associated with multilocular morphology and larger size.

Conclusions: Steroid therapy is an effective choice for cysts developing in AIP to promote the release of pancreatic juice stasis. Larger lesions with multilocular morphology should be monitored closely for cyst-related complications and be considered strong candidates for steroid therapy.     

Identification of the optimal structure required for a Shiga toxin neutralizer with oriented carbohydrates to function in the circulation

Shiga toxin (Stx) is a major virulence factor of Stx-producing Escherichia coli. Recently, we developed a therapeutic Stx neutralizer with 6 trisaccharides of globotriaosyl ceramide, a receptor for Stx, in its dendrimer structure (referred to as "SUPER TWIG [1]6") to function in the circulation. Here, we determined the optimal structure of SUPER TWIG for it to function in the circulation and identified a SUPER TWIG with 18 trisaccharides, SUPER TWIG (2)18, as another potent Stx neutralizer. SUPER TWIGs (1)6 and (2)18 shared a structural similarity, a dumbbell shape in which 2 clusters of trisaccharides were connected via a linkage with a hydrophobic chain. The dumbbell shape was found to be required for formation of a complex with Stx that enables efficient uptake and degradation of Stx by macrophages and, consequently, for potent Stx-neutralizing activity in the circulation. We also determined the binding site of the SUPER TWIGs on Stx.     

Requirement of gp130 signaling for the AGM hematopoiesis

OBJECTIVE: Definitive hematopoiesis starts in the aorta-gonad-mesonephros (AGM) region during mouse development and remarkably expands in the liver at a later stage of ontogeny. gp130 is a signal transducing receptor component shared by all the IL-6 family cytokines, whose gene ablation in mouse results in the significant reduction in the fetal liver hematopoiesis. The present study aims to evaluate the role of gp130 signaling in the fetal mouse AGM hematopoiesis. METHODS AND MATERIALS: Mouse AGM regions from the wild-type and gp130-deficient mice on embryonic day 11.5 were dissociated and cultured with a mixture of cytokines, including one which activates gp130. Wild-type human gp130 and its mutant constructs were introduced into cultured gp130-deficient AGM cells using retrovirus system. To further analyze gp130 downstream signaling, a dominant-negative mutant of STAT3 was also introduced. RESULTS: The gp130 deficiency in the culture of fetal mouse AGM cells resulted in the failure of the expansion of the c-kit(+), Sca-1(+), and lineage markers(-) population. Such failure was rescued by introduction of a wild-type gp130 expression construct but not its mutant constructs having no ability to activate STAT3. In the normal AGM cell culture, introduction of a dominant-negative form of STAT3 in which Y(705) was changed to phenylalanine suppressed the expansion of hematopoietic cell colonies. CONCLUSION: gp130 plays an indispensable role in the expansion of hematopoietic precursor cells in the fetal mouse AGM. In particular, the activation of STAT3 by gp130 is found to be important in this process.     

Different hypersensitivities against homologous proteins of MGL_1304 in patients with atopic dermatitis

Background

Atopic dermatitis (AD) is exacerbated by sweating, and the skin of most patients with AD are resided by Malassezia (M.) fungi. Recently, MGL_1304 produced by Malassezia globosa was identified as the major histamine releasing antigen in human sweat.