Nonmitogenic anti-CD3F(ab')2 fragments inhibit lethal murine graft-versus-host disease induced across the major histocompatibility barrier

We have investigated the in vivo administration of nonmitogenic anti-CD3F(ab')2 fragments for the prevention of lethal graft-vs-host disease (GVHD) in irradiated recipients of fully allogeneic bone marrow cells plus splenocyte (BMS) inocula. Recipients of anti-CD3F(ab')2 fragments administered for 1 mo post-bone marrow transplantation (BMT) had 100% survival without clinical or histopathological evidence of GVHD. Controls given saline injections succumbed by 39 days post-BMT. Similar results were obtained in groups of recipient mice given BMS in which T cells were depleted by in vitro anti-Thy-1.2 plus C' treatment. Further studies were undertaken to define mechanistic differences in the two approaches. Using Ly-5 congenic sources of donor bone marrow and spleen, we determined that anti-CD3F(ab')2 fragments induced TCR modulation and T cell depletion. Mature splenic-derived CD4+ cells were depleted to a greater extent than CD8+ cells. Early post-BMT, recipients receiving injections with control saline had the highest number of CD4+ and CD8+ cells (which may cause GVHD) followed by recipients of anti-CD3F(ab')2 fragments, with the fewest CD8+ cells observed in the anti-Thy-1.2 + C' treated group. CD3+CD4-CD8- cells (which may suppress GVHD generation) were present in higher numbers early post-BMT in recipients given anti-CD3F(ab')2 fragments as compared to recipients given anti-Thy-1.2 + C'-treated BMS. In long term survivors, a mononuclear T cell containing infiltrate without evidence of destruction was observed in sites of GVHD (lung and liver), consistent with a "Quilty" effect, which was not observed in either of the other two groups. Although survivors were tolerant of donor skin grafts and rejected third party grafts, recipients given anti-CD3F(ab')2 fragments but not anti-Thy-1.2 + C'-treated BMS had vigorous anti-host proliferative responses. These results demonstrate that although in vitro anti-Thy-1.2 + C' treatment of BMS (which is highly depletionary) and in vivo administration of anti-CD3F(ab')2 fragments (which is modulatory and less depletionary) are both effective strategies for GVHD, the cellular events involved in achieving GVHD prevention are indeed different.     

Schools as healthful environments: prerequisite to comprehensive school health?

The development of healthy schools to support and nature the well-being of students, teachers, and staff is proposed as a first step toward the goal of comprehensive health education. A focus on healthy schools incorporates elements of an expanded concept of comprehensive health education that demands careful consideration of the physical, psychological, and social environment of the nation's schools--worksite to 51 million (students, teachers, and staff). The active participation of all stakeholders in environmental assessments, health and safety audits, and restructuring of schools is an essential part of the school reform movement. A healthy worksite concept supports the transformation of the school environment to increase "productivity" by enhancing the ability of teachers, staff, and students to function well.     

Osmotic concentration of polypeptides from hemofiltrate of uremic patients

In order to clarify the interactions between various doses of thiopental and fentanyl in producing "balanced anaesthesia", their effects on consciousness, superficial nociception, and respiration and circulation were studied during N2O+O2 inhalation in connection with the induction of anaesthesia. Altogether 60 patients were studied; the drug combinations used were thiopental 5 mg/kg (TP5), thipental 3 mg/kg (TP3), thiopental 3 mg/kg and fentanyl 0.5 micrograms/kg (TP3F0.5), thiopental 2 mg/kg and fentanyl 1 micrograms/kg (TP2F1), thiopental 1 mg/kg and fentanyl 2 micrograms/kg (TP1F2), and fentanyl 3 micrograms/kg (F3). Five minutes after the i.v. supplementation of N2O+O2 anaesthesia, the depth of anaesthesia and analgesia (antinociception) were evaluated from the eyelid reflex and by pinching an inguinal skin fold. Cardiorespiratory parameters were measured during this study period at 1-min intervals. The balance between antinociception and anaesthesia was closest to optimum in groups TP2F1 and TP2F0.5. In pure thiopental groups, the analgesia was poor; only four patients did not respond to the nociceptive stimulus, whereas in group F3 anaesthesia (disappearance of the eyelid reflex) was obtained in only two patients. The respiratory depression was most pronounced in groups receiving 3, 2 and 1 micrograms/kg fentanyl and weakest in groups where only thiopental was used. Blood pressure decreased in all groups but no statistically significant differences were noted. On the basis of the results it seems obvious that attempts to achieve what is called "balanced anaesthesia" by the supplementation of an N2O+O2 mixture with fentanyl only leads to an unnecessarily prnounced respiratory depression, whereas supplementation with thiopental alone does not offer adequate antinociception.     

Steroid-responsive encephalomyelitis in childhood

The syndrome of parainfectious encephalomyelitis evolves from an antecedent infection. Several etiologic agents have been associated with this complication, although the pathogenesis in each instance may prove to be more uniform. Considerable evidence suggests that the syndrome is mediated immunologically. The seven cases reported here were clinically similar, although the infectious etiologies were diverse. Leptospirosis antedated the neurologic syndrome in two cases, and a "viral" illness preceded the other five cases. The evolution of the syndrome was slowly progressive in each case, and six patients had prominent involvement of rhombencephalic structures. The progressive course was reversed rapidly with eventual full recovery in each instance after initiation of corticosteroid therapy. Our experience with these cases coupled with a review of the literature suggests that corticosteroid therapy should be considered in the subacute or chronic cases of parainfectious encephalomyelitis.     

A new method for evaluating antiarrhythmic drug efficacy

To develop standards for distinguishing antiarrhythmic drug effect from spontaneous variability of premature ventricular complexes (PVCs), 21 males (mean age 56 +/- 8 years) with chronic ischemic heart disease and PVCs underwent symptom-limited treadmill exercise testing and 24-hour ambulatory monitoring before and after 2 weeks of placebo medication. Linear regression analysis was used to describe the relationship between baseline and placebo PVC frequency for various indexes of ventricular ectopic activity and to establish 95% and 99% one-tailed confidence intervals for this relationship within the group of 21 patients. The lower limit of baseline PVC frequency for which the procedure could distinguish a placebo from a true drug response, termed the "sensitivity threshold," was an average frequency of 2.2 PVCs/hour for ambulatory electrocardiographic monitoring and 1.2 PVCs/min for treadmill exercise testing. All patients exceeded the sensitivity threshold on baseline ambulatory ECGs, but only 38% of patients did so on baseline treadmill exercise tests. To establish antiarrhythmic efficacy with 95% confidence, the minimal percent reduction of PVCs between baseline and placebo visits was 68% for treadmill exercise testing and 65% for ambulatory electrocardiography. Although these standards were developed in patients with chronic ischemic heart disease, the model can be used to establish antiarrhythmic drug efficacy in any patient group.     

Grafting of enzymes on collagen films using Woodward''s reagent "K" and a water-soluble carbodiimide derivative

Two new methods of activation were developed to graft enzymes on collegen films. They involved chemical modifications of surface groups of collagen either by Woodward's reagent "K" or by EDC, a water-soluble derivative of carbodiimide. EDC was a better coupling agent and a detailed study was conducted with this agent. It could be used either in a global method of activation and coupling, or in a two-step procedure of activation of collagen, followed by spontaneous coupling of enzyme. All enzymes tested were successfully bound: malate dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, urease, creatine kinase, hexokinase. The influence on the yield of grafted enzyme, of pretreatment of films, time and temperature of EDC activation, concentration of EDC and enzyme, protecting agents was studied. Stability of enzyme activity on storage was greatly increased after grafting. A co-grafted dual system creatine kinase/heoxkinase, was achieved which exhibited a good efficiency. A striking renaturing process at 0-4degreesC after thermal denaturation, was observed with hexokinase.     

Low-frequency magnetic interference in a SQUID gradiometer caused by a Cryotiger gas-mixture cooler

A Cryotiger^® gas-mixture cooler was applied for cooling of three high-T_c SQUID magnetometers. These SQUID magnetometers were mounted on an alumina holder in an axial gradiometer configuration. From 20 Hz upward, the system noise was about 0.1 pT/√Hz. Below this frequency, the noise gradually increased to a level of 10 pT/√Hz at 1 Hz. This low-frequency excess noise appeared to be due to remnant magnetization of the Cryotiger cold head. Movement of magnetic cold-head parts with respect to the SQUIDs are induced by pressure fluctuations in the heat exchanger lines. By using one SQUID as a reference for the cooler noise, a first-order gradiometer can be formed in which the cooler noise is eliminated. To establish a proper second-order gradiometer either a fourth SQUID has to be added, or the spatial separation between cold head and SQUIDs has to be increased significantly.     

User preference mining techniques for personalized applications

Advanced personalized e-applications require comprehensive knowledge about their users’ likes and dislikes in order to provide individual product recommendations, personal customer advice, and custom-tailored product offers. In our approach we model such preferences as strict partial orders with “A is better than B” semantics, which has been proven to be very suitable in various e-applications. In this paper we present preference mining techniques for detecting strict partial order preferences in user log data. Real-life e-applications like online shops or financial services usually have large log data sets containing the transactions of their customers. Since the preference miner uses sophisticated SQL operations to execute all data intensive operations on database layer, our algorithms scale well even for such large log data sets. With preference mining personalized e-applications can gain valuable knowledge about their customers’ preferences, which can be applied for personalized product recommendations, individual customer service, or one-to-one marketing.