Neural regulation of compensatory enlargement of the parotid gland of the rat

Summary The role of the innervation in mediating compensatory enlargement of the parotid gland of the rat after partial desalivation was examined. The results of denervation experiments show that full compensatory growth requires both parasympathetic and sympathetic innervation. The presence of the parasympathetic innervation alone results in an increase in the number of cells, but not the size of the cells. The sympathetic innervation alone does not mediate either response. We, therefore, conclude that the two types of innervation have a synergistic action on the parotid to produce the maximal compensatory response, which includes an increase in both number and size of acinar cells.Supported in part by the Veterans Administration and Grant DE 02110 of the U.S. Public Health Service     

Infliximab concentration monitoring improves the control of disease activity in rheumatoid arthritis

Introduction  

Adjustment of infliximab dosage for individuals may be useful in improving therapeutic response in rheumatoid arthritis (RA). Herein, we aimed to determine whether measurement of infliximab serum concentration modifies the therapeutic decision and improves the control of disease activity.     

High apex predator biomass on remote Pacific islands

On coral reefs in Palmyra—a central Pacific atoll with limited fishing pressure—total fish biomass was 428 and 299% greater than on reefs in nearby Christmas and Fanning Islands. Large apex predators, groupers, sharks, snappers, and jacks larger than 50 cm in length, accounted for 56% of total fish biomass in Palmyra on average, but only 7 and 3% on Christmas and Fanning. These biomass proportions are remarkably similar to those previously reported for the remote and uninhabited Northwest Hawaiian Islands (NWHI) and densely populated Main Hawaiian Islands (MHI), although Palmyra’s reefs are dominated in biomass by sharks (44% of the total), whereas the NWHI by jacks (39%). Herbivorous fish biomass was also greater on Palmyra than on Christmas and Fanning (343 and 207%, respectively). These results and previous findings indicate that remote, uninhabited islands support high levels of consumers, and highlight the importance of healthy coral reef ecosystems as reference points for assessment of human impacts and establishment of restoration goals.     

Isolation of a 110 000 molecular weight protein in the purification of the nuclear chick intestinal 1,25-dihydroxyvitamin D-3 receptor

A single protein band of molecular weight 110 000 has been obtained after sodium dodecyl sulfate polyacrylamide gel electrophoresis of purified 1,25-dihydroxyvitamin D-3 (1,25-(OH)₂D-3) receptor from crude nuclear extracts of chick intestinal mucosa, prepared in the presence of the protease inhibitors phenylmethylsulfonyl fluoride and ?-aminocaproic acid. The nuclear extract was subjected to a six-step purification scheme, involving polymin P and ammonium sulfate fractionation, DNA-cellulose affinity chromatography, Sephacryl S-200 gel filtration, blue dextran-Sepharose and a final DNA-cellulose chromatographic step. The receptor was obtained in about 1% yield and was purified approx. 3700-fold from the nuclear extract, as assessed by specific activity. Single peaks were observed with ³H-1,25-(OH)₂D-3-labeled crude nuclear extracts on Sephacryl S-200 gel filtration ($\text{Strokes′ radius}\text{= 35.5}\text{A}\text{?}$) and sucrose density gradient centrifugation (3.5 S). Although the identity of the M_r 110 000 protein will remain inconclusive until methods for further characterization are available, it may represent evidence for a higher molecular weight form of the 1,25-(OH)₂D-3 receptor than that observed previously.     

Efficacy and Safety Assessment of the Addition of Bevacizumab to Adjuvant Therapy Agents in Cancer Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Aim

To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients.

Methods & Design/ Results

PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials comparing bevacizumab and adjuvant therapy with adjuvant therapy alone published from January 1966 to 7^th of May 2014. Progression free survival, overall survival, overall response rate, safety and quality of life were analyzed using random- or fixed-effects models according to the PRISMA guidelines. We obtained data from 44 randomized controlled trials (30,828 patients). Combining bevacizumab with different adjuvant therapies resulted in significant improvement of progression free survival (log hazard ratio, 0.87; 95% confidence interval (CI), 0.84–0.89), overall survival (log hazard ratio, 0.96; 95% CI, 0.94–0.98) and overall response rate (relative risk, 1.46; 95% CI: 1.33–1.59) compared to adjuvant therapy alone in all studied tumor types. In subgroup analyses, there were no interactions of bevacizumab with baseline characteristics on progression free survival and overall survival, while overall response rate was influenced by tumor type and bevacizumab dose (p-value: 0.02). Although bevacizumab use resulted in additional expected adverse drug reactions except anemia and fatigue, it was not associated with a significant decline in quality of life. There was a trend towards a higher risk of several side effects in patients treated by high-dose bevacizumab compared to the low-dose e.g. all grade proteinuria (9.24; 95% CI: 6.60–12.94 vs. 2.64; 95% CI: 1.29–5.40).

Conclusions

Combining bevacizumab with different adjuvant therapies provides a survival benefit across all major subsets of patients, including by tumor type, type of adjuvant therapy, and duration and dose of bevacizumab therapy. Though bevacizumab was associated with increased risks of some adverse drug reactions such as hypertension and bleeding, anemia and fatigue were improved by the addition of bevacizumab.     

Diffusion and Topological Neighbours in Flocks of Starlings: Relating a Model to Empirical Data

Moving in a group while avoiding collisions with group members causes internal dynamics in the group. Although these dynamics have recently been measured quantitatively in starling flocks (Sturnus vulgaris), it is unknown what causes them. Computational models have shown that collective motion in groups is likely due to attraction, avoidance and, possibly, alignment among group members. Empirical studies show that starlings adjust their movement to a fixed number of closest neighbours or topological range, namely 6 or 7 and assume that each of the three activities is done with the same number of neighbours (topological range). Here, we start from the hypothesis that escape behavior is more effective at preventing collisions in a flock when avoiding the single closest neighbor than compromising by avoiding 6 or 7 of them. For alignment and attraction, we keep to the empirical topological range. We investigate how avoiding one or several neighbours affects the internal dynamics of flocks of starlings in our computational model StarDisplay. By comparing to empirical data, we confirm that internal dynamics resemble empirical data more closely if flock members avoid merely their single, closest neighbor. Our model shows that considering a different number of interaction partners per activity represents a useful perspective and that changing a single parameter, namely the number of interaction partners that are avoided, has several effects through selforganisation.     

Characterization of Fetal Antigen 1/Delta-Like 1 Homologue Expressing Cells in the Rat Nigrostriatal System: Effects of a Unilateral 6-Hydroxydopamine Lesion

Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been suggested as a potential supplementary marker of dopaminergic neurons. The present study aimed at investigating the distribution of FA1/dlk1-immunoreactive (-ir) cells in the early postnatal and adult midbrain as well as in the nigrostriatal system of 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc dopaminergic neurons and/or due to the stab wound. Our findings hint to a significant role of FA1/dlk1 in the SNc during early postnatal development. The differential expression of FA1/dlk1 in the SNc and the striatum of dopamine-depleted rats could indicate a potential involvement of FA1/dlk1 in the cellular response to the degenerative processes.