Characterization of a monoclonal antibody recognizing mast cells

Immunohistochemical screening for monoclonal antibodies prepared by immunization of mice with a rat osteoblastic cell population led to identification of one antibody that reacted against a small population of cells present in the soft connective tissue compartment of 21 days fetal rat calvaria. The morphology of the cells and the immunohistochemical staining characteristics (a distinct intracellular granular pattern) suggested that the antibody might be reacting specifically against mast cells. We used combined histochemistry and immunohistochemistry to further characterize this antibody, designated RCJ102. Cryosections containing calvaria bone, soft connective tissues and skin were prepared from the top of the head of 21 days fetal rats, and from adult rats cryosections of lung, muscle, adipose tissue and small intestine were prepared. Some sections were labelled by indirect immunofluorescence with RCJ102; corresponding sections were labelled histochemically with toluidine blue. There was a direct correspondence between mast cells identified histochemically and cells labelling with RCJ102 in all tissues except intestine, in which the mast cell detectable by histochemistry were not labelled by RCJ102. These results suggest that the RCJ102 antibody will be a valuable new reagent for further elucidation of the heterogeneity described between connective tissue and intestinal mucosal mast cells.     

Acute eosinophilic pneumonia in a pregnant woman

Acute eosinophilic pneumonia is a recently described pulmonary phenomenon involving rapidly progressing respiratory insufficiency. Although it can appear at any age, it has never been reported during pregnancy and its impact on gestation is therefore unknown. We describe the clinical signs and course of disease in this first report of acute eosinophilic pneumonia in a pregnant woman. We emphasize the diagnostic utility of bronchoalveolar lavage, the resolution of symptoms without corticoid treatment and, mainly, the absence of adverse repercussions of the disease on pregnancy.     

Transdermal nitroglycerin: clinical and pharmacokinetic consequences of renewing the patch and the application site

OBJECTIVE: We examined whether nitroglycerin (glyceryl trinitrate, GTN) patch treatment for 24 h could induce local cutaneous changes that impaired drug delivery and clinical efficacy. METHODS: Twenty angina patients were exercise-tested after 2 and 24 h of treatment and then 2 h after patch renewal. The patch was either renewed on a new skin location or on the previous application site in a randomised, double-blind, cross-over protocol. GTN plasma concentrations and finger plethysmography were obtained before and after each exercise test. RESULTS AND CONCLUSIONS: The clinical efficacy, the effect seen on plethysmography and the GTN plasma concentrations tended to increase after patch renewal, regardless of the application site of the renewed patch. Hence, cutaneous changes of clinical importance could not be demonstrated.     

Symptomatic improvement following emergency department management of asthma: a pilot study of intramuscular dexamethasone versus oral prednisone

Systemic corticosteroid therapy is an established adjunct to beta-adrenergic medications in acute exacerbations of asthma. To date, no study has defined the role of long-acting intramuscular preparations of corticosteroids in pediatric patients with asthma. A pilot study was conducted to prospectively compare symptomatic improvement following a single injection of intramuscular dexamethasone (IMD) to a 3-day regimen of oral prednisone (OP) for children with mild to moderate wheezing episodes that are responsive to nebulized medications in the Pediatric Emergency Department (PED). The following children presenting with acute exacerbations of asthma to the PED were eligible for enrollment: age 3-16 years; more than two prior wheezing episodes; mild to moderate wheezing; and oxygen saturation 95% or more in room air. The study patients were randomly assigned to receive either IMD (n = 21) or OP (n = 21) in addition to a standardized treatment regimen of nebulized albuterol. All of the children were clinically rated for wheezing severity by the Pulmonary Index (PI) score at regular intervals during the study. Discharge home was based on clinical improvement during treatment in the PED; patients who were admitted to the hospital were removed from the study. Follow-up was conducted the fifth day after discharge from the ED either by clinic visit or by telephone. Patients were assessed for symptomatic improvement and relapse or clinical deterioration during the study period by a clinician blinded to group assignment. Forty-two children participated in this pilot study. There were no significant differences between the IMD and OP groups for gender or age. Mean ages were: 82 months (SD 46 months), IMD group; 63 months (SD 36 months), OP group. Clinical progress (based on PI) with treatment in the PED was the same in both groups: pretreatment median, PI = 6; PED discharge median, PI = 2. None of the study patients were hospitalized during the follow-up period, and all reported symptomatic improvement since initial treatment. The data of this pilot study suggest that IMD may be a feasible alternative to OP for treatment of acute wheezing episodes in children with asthma. IMD provides sufficient treatment to prevent clinical deterioration within 5 days after initial therapy for mild to moderate pediatric exacerbations of asthma that are responsive to nebulized medications.     

The NIDDK liver transplantation database

Gap junctional communication between glial cells is thought to play a role in K+ spatial buffering, in the propagation of inter-astrocytic Ca2+ waves, and in glial-neuronal signaling. In the present study, we characterize dye coupling between astrocytes, and between astrocytes and Müller cells, in the isolated rat retina. Whole-cell patch recordings were obtained from retinal astrocytes and Müller cells and the cells filled with Lucifer Yellow and neurobiotin. Spread of Lucifer Yellow to two to ten neighboring astrocytes occurred in 90% of the astrocyte recordings. After fixation and incubation of the retina with fluorescent conjugated streptavidin, neurobiotin was seen to label clusters of 13-88 astrocytes, as well as > 100 Müller cells. In contrast, when Müller cells were filled with Lucifer Yellow and neurobiotin, both tracers were confined solely to the recorded Müller cell. The uncoupling agents octanol, halothane, and doxyl-stearic acid were tested for their ability to uncouple retinal glia in situ. All three agents eliminated the visible spread of Lucifer Yellow from the injected astrocyte and the spread of neurobiotin into Müller cells. However, only doxyl-stearic acid combined with octanol eliminated the spread of neurobiotin between astrocytes. These results demonstrate that astrocytes in the rat retina are coupled to each other and to Müller cells. The astrocyte-to-Müller cell coupling is asymmetric, allowing transfer of the tracer in the forward direction only. In addition, astrocyte-to-Müller cell coupling is more sensitive to the uncoupling agents tested than is astrocyte-to-astrocyte coupling.     

Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory

Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4-month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.