Expression and characterization of a cytotoxic human-frog chimeric ribonuclease: potential for cancer therapy

Onconase is a cytotoxic ribonuclease with antitumor properties. A semisynthetic gene encoding the entire protein sequence was constructed by fusing oligonucleotides coding for the first 15 and last six of the 104 amino acid residues to a genomic clone that encoded the remaining amino acid residues. Additionally, the 15 N-terminal amino acid residues of onconase were replaced with the first 21 amino acid residues of the homologous human RNase, eosinophil-derived neurotoxin, EDN. Two versions of the hybrid EDN-onconase protein were cloned, expressed and purified. The chimera that contained a glycine in lieu of the aspartic acid present in native onconase (position 26 in the chimera) exhibited enzymatic activity more characteristic of EDN than native onconase and was considerably more active with respect to both RNase activity and cellular cytotoxicity than recombinant onconase. In contrast to native or recombinant onconase, the EDN chimera was recognized by anti-EDN polyclonal antibodies, demonstrating that the chimera also shared structural antigenic determinants to the human enzyme. These results demonstrate that a chimeric ribonuclease has cytotoxicity comparable to onconase in two out of four cell lines tested. The implications with regard to cancer therapy are presented.      

Multimedia and firewalls: a performance perspective

Firewalls are a well-established security mechanism to restrict the traffic exchanged between networks to a certain subset of users and applications. In order to cope with new application types like multimedia, new firewall architectures are necessary. The performance of these new architectures is a critical factor because Quality of Service (QoS) demands of multimedia applications have to be taken into account. We show how the performance of firewall architectures for multimedia applications can be determined. We present a model to describe the performance of multimedia firewall architectures. This model can be used to dimension firewalls for usage with multimedia applications. In addition, we present the results of a lab experiment, used to evaluate the performance of a distributed firewall architecture and to validate the model.     

Trajectory planning for quasilinear parabolic distributed parameter systems based on finite-difference semi-discretisations

In this contribution, a flatness-based approach is considered for the solution of the trajectory planning problem for quasilinear parabolic distributed parameter systems (DPS) by making use of finite-difference semi-discretisations. It is shown that the method yields solutions which are equivalent to results known from the infinite-dimensional trajectory planning for a certain class of quasi-linear parabolic DPS. Furthermore, the methodology being proposed can also be applied to systems with general analytic nonlinearities. As analytical convergence results are not available in this case, a numerical test criterion for the convergence behaviour is suggested.     

The Role of Social Network Sites in Romantic Relationships: Effects on Jealousy and Relationship Happiness

On social network sites (SNS), information about one's romantic partner is readily available and public for friends. The paper focuses on the negative (SNS jealousy) and positive (SNS relationship happiness) consequences of SNS use for romantic relationships. We examined whether relationship satisfaction, trait jealousy, SNS use and need for popularity predicted these emotional consequences of SNS use and tested the moderating role of self‐esteem. For low self‐esteem individuals, need for popularity predicted jealousy and relationship happiness. For high‐self‐esteem individuals, SNS use for grooming was the main predictor. Low‐self‐esteem individuals try to compensate their low self‐esteem by creating an idealized picture. Undesirable information threatens this picture, and especially individuals with a high need for popularity react with SNS jealousy.     

1,25-Dihydroxyvitamin D3 prolongs graft survival without compromising host resistance to infection or bone mineral density

BACKGROUND: Recently, we have shown that 1,25-dihydroxyvitamin D3 prolongs graft survival in mice and rats when the donor and recipient differ at two or more major histocompatability loci. Among the most serious side effects encountered with the currently available transplantation antirejection drugs are an increased susceptibility to infection and decreased bone mineralization. Our results suggest that 1,25-dihydroxyvitamin D3 prolongs graft survival without these side effects of bone loss and susceptibility to infection. METHODS: We compared the ability of 1,25-dihydroxyvitamin D3-treated, nontreated, or cyclosporine (CsA)-treated mice to resist infection with Candida albicans and herpes simplex virus-1. To determine bone density, femurs were collected from nontreated, 1,25-dihydroxyvitamin D3-treated (50 ng/mouse/day), or CsA-treated (25 mg/kg/day) mice, and bone ash was determined. RESULTS: Here we show that 1,25-dihydroxyvitamin D3 treatment does not increase the susceptibility of the host to fungal or viral infection. Furthermore, CsA causes bone loss, whereas 1,25-dihydroxyvitamin D3 actually increases bone mass. CONCLUSIONS: The use of 1,25-dihydroxyvitamin D3 and its analogs to increase transplant survival will avoid bone loss and opportunistic infection, two important disadvantages of the most widely used transplant antirejection drugs--CsA and the glucocorticoids.     

Clock-face drawing, reading and setting tests in the screening of dementia in Chinese elderly adults

Comprehensive neuropsychological batteries focus on the subtle cognitive deficits in dementia, but a brief screening instrument is also of immense practical value. As the clock-drawing test encompasses a number of cognitive domains frequently disturbed by the dementing process, it is considered to be a suitable screening instrument for the disorder. We documented the usefulness of a new scoring method of the clock-drawing test for screening of dementia in the elderly Chinese in Hong Kong. Fifty-three demented individuals and 53 healthy elderly controls were assessed. At a cutoff score of 3/4, the sensitivity and specificity of the clock-drawing test in screening of dementia was 83% and 79%. With a composite test of clock reading and clock setting, the positive predictive value of the clock face test was 98%. This new scoring method of clock-drawing proved to be a valid measure for screening of dementia. It is applicable in non-English speaking populations and should be a useful adjunct for quick screening assessment of dementia.     

Changing practice patterns in peripheral arterial disease

The development of interventional radiologic techniques during the past decade has changed our approach to the treatment of lower extremity peripheral arterial disease (LE-PAD). Balloon and laser-assisted angioplasty, atherectomy (rotary and directional devices), stent implantation, and thrombolysis as well as combinations of all of these approaches, at times with concomitant or secondary surgery, have been used in our institution. A review of our practice patterns during the past 5 years was performed to analyze changing attitudes and results with these newer techniques. All new patients seen in consultation for LE-PAD during three alternate years were reviewed with regard to demographics, initial complaints, initial treatment modality, initial outcome, indications for and results of secondary treatment, and ultimate outcome (at 1 year). The 603 patients were seen during the following three 12-month periods: 1987 to 1988, 1989 to 1990, and 1991 to 1992. An intention-to-treat analysis revealed (1) the number of patients seen for peripheral arterial disease has increased steadily; (2) in the last year more were initially treated with intervention as the primary modality; (3) the results of such catheter-based procedures improved only slightly over this 5-year period, despite our learning curve and the fact that we discarded several ineffective interventional approaches; (4) the fraction of patients primarily operated on and the excellent results of surgery have not changed; and (5) the number of operations for proximal (aortoiliac) disease has decreased markedly, with a corresponding increase in distal reconstructions. The evolution of our current approach to the treatment of LE-PAD is based on this continuing experience.     

HLA antigens in patients with giant cell arteritis and polymyalgia rheumatica

The frequency of 24 HLA antigens was determined in 43 patients with giant cell arteritis (25 of whom had polymyalgia rheumatica) and 12 others with polymyalgia rheumatica without evident arteritis. No haplotype was present in significantly increased frequency above controls in the total group nor when the patients were separated according to the presence or absence of polymyalgia rheumatica.     

Qualitative analysis of fetal movement patterns in the Neu-Laxova syndrome

In some previous studies, acute administration of some antidepressants has been reported to cause significant changes in the levels of blood glucose and insulin in the rabbit. In the present study the effects of several antidepressants representing classical groups of antidepressants, namely imipramine (CAS 50-49-7, I), maprotiline (CAS 10347-81-6, M) and bupropion (CAS 34911-55-2, (B) on insulin secretion from the isolated islets of Langerhans in mice was studied. Maprotiline and bupropion stimulated insulin release, while imipramine was without any effect in presence of 8.3 mmol/l glucose. On the other hand, in presence of 16.7 mmol/l imipramine and maprotiline suppressed the stimulated insulin secretion. Bupropion inversely significantly stimulated the insulin secretion in presence of 16.7 mmol/l glucose. It is concluded that the changes of blood glucose and plasma insulin observed in vivo may at least in part be due to respective changes of insulin secretion. The treatment of diabetic patients receiving antidepressant drugs with hypoglycaemic agents should be taken in consideration.