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.     

Use of Graduate Study in Psychology as a data source.

Comments on an article by C. M. Stoup and L. T. Benjamin, Jr. (see record 1983-24200-001), in which they used various editions of Graduate Study in Psychology, published by the American Psychological Association (APA), to report the GPAs and Graduate Record Examination scores of master's and doctoral students across various areas of psychology. It is cautioned that the use of Graduate Study in Psychology as a data source calls for skepticism, as there is sufficient reason to question some of the data that are submitted to the APA by psychology departments. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

The fine structure of the interrenal cells of the duck (Anas platyrhynchos) with evidence for possible exocytotic release of steroids

The duck interrenal cell possesses ultrastructural characteristics common to other steroid-secreting cells. Lipid droplets and mitochondria are abundant and lie principally at the apical end of the cell. Lipid droplets are not membrane-limited. Cisternae of smooth endoplasmic reticulum that are occasionally continuous with the less abundant rough endoplasmic reticulum are a prominent feature of the interrenal cell. Tubular profiles of rough endoplasmic reticulum often lie tangentially to mitochondria and ribosomes are either free, grouped in polyribosomal clusters, or bound to the endoplasmic reticulum. Mitochondria possess tubular cristae in the inner regions of the gland and frequently contain a paracrystalline array of small 10nm (o.d.) tubules and less frequently a hexagonal array of 40 nm trilaminar rings. Other cytoplasmic components include dense bodies, residual bodies, microtubules, microfilaments and specialized single membrane-bound vesicles. Gap junctions, intermediate junctions and interdigitating processes constitute the main intercellular associations. No tight junctions were identified. The single membrane-bound vesicles which are occasionally filled with a low electron-dense, lipid-like material form septate-like "junctions" with the plasma membrane. The septa bridge an intracellular gap of 15-17 nm. The vesicles are usually located near the subendothelial space at the basal and basilateral regions of the cell. Occasionally, vesicles fuse with the plasma membrane. It is suggested that these vesicles represent morphological evidence for the exocytotic release of steroid hormones.     

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.     

The turnover and distribution of labelled corticosterone during post-natal development of the duckling (Anas platyrhynchos)

During 6 months of post-natal development in the laboratory, the weight of the adrenal gland relative to body weight decreases exponentially. In the 3 day-old duckling a single intravenous dose of labelled corticosterone becomes distributed in a very large apparent volume and an "extracellular" pool that is greater than the extracellular fluid volume and the pattern of disappearance of labelled hormone from plasma is biphasic. Later during development the volumes of distribution decrease and the biphasic pattern of disappearance becomes less distinct until at 6 months only one phase of disappearance can be detected with confidence. No significant change in plasma corticosterone concentration occurs during this period of development in the laboratory. Estimations of the corticosterone secretory rates, however, indicate that whereas the adrenal weight-specific rate os secretion increases during the first 3 weeks and declines therafter, the bodyf weight-specific secretory rate continues to decline throughtout the period of increasing body weight.