Prolactin variants in ram adenohypophyses vary with season.

Secretion of PRL in sheep is affected by photoperiod being highest during the spring and summer, lowest in fall and winter. The objectives of this study were to determine if 1) the production of variant forms of PRL, and 2) immuno- and bioactivities of PRL (iPRL and bPRL) differ during times of the year selected to represent periods of low, transitional and high PRL secretion. Twelve mature rams were maintained on pasture and killed in October, December, and April (n = 4/month). Individual pituitary glands were dispersed, cells obtained, and fixed for immunocytochemical flow cytometry, extracted with 0.01 N NaHCO3 or cultured in serum-free, defined media. The Mr of PRL extracted from cells immediately following dispersion ranged from 14-140K, with significantly more bands greater than 40K being detected from rams sacrificed in December than from those killed in October and April (P less than 0.01). No bands of PRL greater than 25K were observed when samples were reduced with beta-mercaptoethanol prior to electrophoresis, indicating that the high Mr forms were disulfide-linked aggregates. Culture media from October and April contained variants of PRL that ranged from 22-40K but those greater than 25K were generally not observed from cells harvested during December. Extracts of cells after 24 h in culture contained fewer high Mr species during December than had been present in initial extracts from that month. In contrast, during April more high Mr intracellular forms were present after culture than had been detected prior to culture during that month. The percentage of lactotrophs averaged 50.0 +/- 2.5, 47.4 +/- 5.7, and 59.4 +/- 5.5 for October, December, and April, respectively. Initial lactotroph content (pg/lactotroph) of iPRL was higher (P = 0.06) in April (46.0 +/- 17.0) when compared to October and December (8.0 +/- 2.0 and 20.0 +/- 10.0, respectively). In contrast, the bPRL content of initial extracts was higher (P = 0.05) in December (267.0 +/- 68.0) than in October (101.0 +/- 35.0), but not than in April (190.0 +/- 70.0). Although iPRL and bPRL concentrations in culture media were similar for the 3 months, the intracellular iPRL (P less than 0.001) and bPRL (P less than 0.0001) content after culture was greatest during April. In summary, in addition to the well-documented seasonal changes in blood concentrations of PRL, different molecular forms of PRL were found within the pituitary at different times of the year and seasonal variations in iPRL and bPRL did not occur in parallel.     

B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus

We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.     

Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.     

术中大剂量放疗治疗局部复发头颈癌

该文旨在介绍Beth Israel医疗中心采用大剂量术中放疗(HDR-IORT)治疗复发头颈癌的经验。对2001-2010年间头颈癌局部复发接受大剂量HDR-IORT的患者进行回顾分析。结果,76例患者的87个部位在肿瘤切除后接受了治疗。术后2年控制率为62%。平均总生存期为19个月,其中42%的患     

Changes in plasma profiles of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in stress-induced cardiomyopathy

BackgroundTransient changes in the composition of the myocardial extracellular matrix may contribute to the ventricular systolic dysfunction in stress-induced cardiomyopathy (SIC). We examined the changes in plasma matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) that occur early after the clinical presentation of SIC.Methods and ResultsTen patients with SIC were enrolled. Plasma concentrations of the 6 major MMPs (1, 2, 3, 7, 8, and 9) and all 4 TIMPs (1, 2, 3, and 4) were analyzed and compared with data from 15 control subjects. Within 24 hours of the clinical presentation, SIC patients had lower MMP-1 levels (0.41 ± 0.13 vs 0.70 ± 0.13 pg/mL; P = .048) and MMP-8 levels (1.61 ± 0.34 vs 4.84 ± 1.38 pg/mL; P = .001) and higher TIMP-4 levels (3.06 ± 0.40 vs 2.16 ± 0.18 pg/mL; P = .05) compared with control. Seven of 9 SIC patients had elevated LV end-diastolic pressures, and all had normal LV end-diastolic dimensions and volumes.ConclusionsPatients afflicted with SIC had MMP and TIMP profiles similar to those described in hypertensive heart disease and diastolic heart failure and different from the profiles following myocardial infarction. Our findings uncovered a unique biomolecular profile in SIC during the first 24 hours of presentation.     

Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Background

Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.

Methods

The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.

Results

Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.

Conclusions

In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.