Antimicrobial activity of various immunomodulators: independence from normal levels of circulating monocytes and natural killer cells.

The effects of 89Sr treatment on the natural host resistance of CD-1 mice and the enhancement of resistance by immunomodulators to infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) were determined. In the CD-1 mouse, single-dose treatment with 89Sr caused a profound decrease in the number of circulating monocytes (Mo), lymphocytes, and polymorphonuclear leukocytes (PMN) within 1 week. There was also marked functional impairment of the Mo inflammatory response, as well as markedly decreased spontaneous and activatable cytotoxicity by splenic natural killer (NK) cells. Despite this profound cellular suppression, there was no significant change in natural resistance of CD-1 mice to L. monocytogenes or HSV-2 infection. Furthermore, prophylactic treatment of mice with the biologic immunomodulator Corynebacterium parvum or the synthetic immunomodulators maleic anhydride-divinyl ether or avridine in liposomes resulted in comparable enhancement of resistance in 89Sr-treated and normal mice. These data indicate that natural and immunomodulator-enhanced resistance of CD-1 mice to microbial infections do not depend on normal levels of Mo, PMN, or NK cells. The resistance enhancement may rely on activated tissue macrophages (M phi). In contrast to the early changes in circulating leukocytes, the resident peritoneal cell populations were not markedly altered until after day 30. There then was a distinct decline in lymphocytes and a gradual decline in M phi; the change in M phi was apparently due to the lack of an age-related increase in the peritoneal M phi population in 89Sr-treated mice in comparison with a slight increase in resident M phi in normal mice. After CD-1 mice were treated with 89Sr, the number of PMN and the function of NK cells generally recovered by about day 50 and was followed by partial recovery of circulating Mo, unless a second dose of 89Sr was administered.     

Neurobehavioral Symptoms and Family Functioning in Traumatically Brain-Injured Adults

Traumatic brain injury (TBI) often results in a myriad of symptoms across physical, cognitive, and neurobehavioral domains. Despite inherent limitations associated with physical or cognitive impairments, the extant literature suggests that neurobehavioral symptoms tend to be the most distressing symptoms for the family and are more strongly related to poor outcome for the patient. The Neuropsychology Behavior and Affect Profile (NBAP) along with the General Functioning subscale of the Family Assessment Device (FAD-GF) and the Perceived Stress Scale were administered to 153 family members of persons who had sustained a TBI. The results provide new normative data and statistical support for the NBAP as a promising measure of neurobehavioral symptomatology following TBI. The correlation of.54 (p <.01) between FAD-GF and Full Scale NBAP scores provides powerful support for the hypothesis that family dysfunction is related to the presence of neurobehavioral symptoms in the patient. NBAP domains of Depression, Inappropriateness, Pragnosia, and Indifference appear most strongly related to family functioning and also bear a significant relationship to caregiver stress level and patient unemployment, whereas injury severity had little impact on either family functioning or neurobehavioral symptoms. The findings reinforce the significance of neurobehavioral symptoms and fortify their proposed link to family dysfunction post-TBI.     

T cell subsets in idiopathic glomerulonephritis

Determination of T lymphocyte subsets using monoclonal antibodies revealed a deficiency of suppressor cells and an elevated helper:suppressor T cell ratio in 7 patients with untreated idiopathic immune complex glomerulonephritis and nephrotic syndrome. Possible pathogenetic mechanisms of immunoregulatory cell imbalance and their implications specifically in reference to idiopathic glomerulonephritis are discussed.     

Total serum IgD is increased in atopic subjects

We have developed a sandwich-type ELISA system for measuring total IgD levels in the serum of atopics and non-atopic controls. In this ELISA system, affinity purified goat anti-human IgD was used for capture. Results were superior to those obtained with monoclonal anti-human IgD antibody. No cross-reactivity could be demonstrated to IgG, IgM, IgA or IgE. The assay showed minimal non-specific binding even with initial serum dilutions of 1:2. The results obtained were reproducible among replicates (Mean CV +/- SEM = 0.03 +/- 0.002; n = 251), between dilutions (CV = 0.08 +/- 0.006; n = 108), and between assays (CV = 0.05 +/- 0.12; n = 5). We used routine radioimmunoassay for measuring total serum IgE. Using these assays total serum IgD and IgE levels were measured in 75 atopic patients and 33 normal subjects. None of the atopics had recent immunotherapy. As expected, the geometric mean serum IgE in atopics (373 ng/ml) was significantly higher than that in normal subjects (49 ng/ml) (P less than 0.01). However, geometric mean serum IgD was also significantly higher in atopics (20.3 micrograms/ml) than that in normal subjects (8.4 micrograms/ml) (P less than 0.02). In both atopic and normal groups, mean serum IgD level did not differ significantly on the bases of age, sex or asthmatic status. Furthermore, total serum IgD was not significantly correlated with total serum IgE (r = 0.14; P = 0.14; n = 108), indicating that immunoregulatory control of the basal levels of the two isotypes is not linked.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

A three generation family with fibrodysplasia ossificans progressiva.

A family with five persons affected with fibrodysplasia ossificans progressiva (myositis ossificans progressiva) in three generations is described. This is the first well documented three generation family with this condition and provides further evidence for autosomal dominant inheritance. A wide range of phenotypic severity is apparent, from disabling ectopic bone formation and premature death to an asymptomatic adult with characteristic big toe malformations.