Relationship between numbers of beta adrenergic receptors in lymphocytes and disease severity in asthma

In order to assess the status of beta adrenergic receptors in bronchial asthma, binding studies using (−) [³H] dihydroalprenolol (DHA) were performed on lymphocytes of 10 control subjects and 11 stable asthmatic patients. Specific DHA binding was generally lower at all DHA concentrations in asthmatics. At 12 nM DHA concentration, specific DHA binding was 391 ± 40 fM/mg protein in controls and 263 ± 35 fM/mg protein for asthmatic subjects (p < 0.05). A highly statistically significant positive correlation between specific DHA binding (at 12 nM DHA) and FEV₁/FVC% was observed (r = 0.93, p < 0.01), with those asthmatic subjects with the more severe airway obstruction and disease severity showing lower DHA binding. The results of the study suggest that a lymphocyte beta adrenergic receptor defect may be present among some patients with asthma. The magnitude of the receptor abnormality appears to be related to disease severity and degree of airway obstruction as measured by FEV₁/FVC%. Documentation of drug consumption was made, and restriction of beta adrenergic agonists was attempted; theophylline and corticosteroids were the predominant drugs used in the study. Even with these precautions, it is possible that the differences in DHA binding observed among subjects are the results of greater drug (e.g., theophylline and corticosteroids) consumption by the clinically more severe patients. On the other hand, the lymphocyte receptor alteration noted may reflect a more general beta adrenergic receptor abnormality in bronchial asthma.     

Brief report: cautions against using the Stanford-Binet-IV to classify high-risk preschoolers

OBJECTIVE: To explore concurrent and predictive validity of the Stanford-Binet: Fourth Edition (SB-IV) by comparing scores on the SB-IV with scores from the Battelle Developmental Inventory (BDI) and later achievement scores in preschoolers at risk due to very low birthweight, and/or intraventricular hemorrhage (IVH) and other medical complications. METHODS: At ages 3,4, and 5, 92 preschoolers were tested with the SB-IV and BDI as part of an 8-year early intervention follow-up. RESULTS: The SB-IV and BDI concurrent correlations at ages 3, 4, and 5 were statistically significant (r = .73-.78, p < .0001), as were predictive correlations (r = .58-.85, p < .0001). However, the BDI and SB-IV failed to place the children in the same categories for intervention services. With the BDI as the comparison measure, SB-IV failed to detect 87% of the children who were "delayed" (by BDI) at age 3 and 50% of the "delayed" children at age 5. CONCLUSIONS: Caution is recommended when using the SB-IV to assess high risk for early intervention eligibility.     

Enzyme histochemical localization of Na+,K+‐ATPase and NADH‐DE in the developing rat parotid gland

Information on ductal differentiation in the developing rat parotid gland is sparse. Striated and excretory ducts are rich in a number of enzymes related to ion movement. The objective of this investigation was to delineate histochemically the chronology of two of these, ouabain‐sensitive Na⁺,K⁺‐ATPase and NADH‐DE, in the developing rat parotid gland. Parotid glands were excised from rats at representative ages from 20 days in utero to 42 days. Enzyme histochemistry was performed on air‐dried frozen sections. For Na⁺,K⁺‐ATPase, some sections also were fixed in phosphate‐buffered formalin. Ouabain blocked Na⁺,K⁺‐ATPase activity, and neither enzyme reacted without substrate. Weak Na⁺,K⁺‐ATPase reactions were initially seen in unfixed sections at 1 day, and increased steadily to the adult pattern of strong (concentrated basolaterally) in striated ducts and excretory ducts, respectively, and weak to modest (diffuse) in acini and intercalated ducts at 28 days. In fixed sections, localization was sharper but the reaction was somewhat reduced. NADH‐DE was modest in terminal buds and ducts before birth, then progressively changed to the adult pattern of weak in acini and intercalated ducts and strong (concentrated basally and luminally) in striated and excretory ducts at 28 days. As demonstrated by enzyme histochemistry of Na⁺,K⁺‐ATPase and NADH‐DE, differentiation of rat parotid striated ducts and excretory ducts occurs mainly between birth and 28 days. Anat Rec 256:72–77, 1999. Published 1999 Wiley‐Liss, Inc.     

Alterations in regulatory behaviors induced by medial septal lesions and superior cervical ganglionectomy

Following medial septal (MS) lesions peripheral sympathetic fibers, orginating from the superior cervical ganglia (SCG), grow into the hippocampus and habenula. To assess their effect on regulatory behaviors, body weight, and food and water consumption were studied under ad libitum and pharmacological stress conditions, after MS lesions, superior cervical ganglionectomy (Gx) or MS lesion + ganglionectomy (MSGx). Twenty-two animals completed the study: control (n = 7), MS lesion (n = 6), Gx (n = 6), MSGx (n = 4). No differences were observed preoperatively. Postoperatively, body weight fell but over time all groups gained weight. However, animals with MSGx were lighter than MS or Gx animals (which were equivalent), which in turn were lighter than controls (P < 0.0001). Hypophagia was observed in the Gx and MSGx animals when compared to the MS and control groups (P < 0.05), while hyperdipsia was seen in the MS and Gx groups (P < 0.001). Administration of both 1 M NaCl and isoproterenol (25 μg/kg) increased drinking in all animals (P < 0.001), with the MSGx group consuming significantly less than all others (P < 0.025). Food intake increased following 2-deoxy-d-glucose (500 mg/kg) (P < 0.0001), while epineprine (120 μg/kg) treatment produced anorexia only in the MS group (P < 0.05). Hyperthermia was found in the Gx and MSGx groups. The results of this study suggest that both MS region and SCG contribute to the maintenance of normal regulatory behaviors, with combined loss of these neural systems resulting in severe disturbances, both qualitatively and quantitatively different from either MS lesion or Gx. Although the MS lesion group clearly regulated better than the MSGx group, it is unclear whether this is due to ingrowth or just the presence of the SCG.     

Hippocampal sympathetic ingrowth and cholinergic denervation alter hippocampal muscarinic cholinergic receptors

Cholinergic denervation of the hippocampus by medial septal (MS) lesions results in the ingrowth of peripheral sympathetic fibers, originating from the superior cervical ganglia, into the hippocampus. To determine the effect of hippocampal sympathetic ingrowth (HSI) [³H]-QNB (L-quinuclidinyl [benzilic-4, 4(n)] benzilate) binding was assessed in the dorsal and ventral hippocampus four weeks after MS lesions. In dorsal hippocampus, HSI was found to signignificantly increase the number (B_max) of [³H]-QNB binding sites and to normalize the decrease in affinity found in animals with MS lesions plus ganglionectomy (i. e., no ingrowth). In ventral hippocampus, HSI was found to normalize the increased number of binding sites and decreased affinity found in animals with MS lesions without ingrowth. No effect on either K_d or B_max was found in animals that had undergone ganglionectomy with sham MS lesions. These results suggest that HSI can induce changes in hippocampal muscarinic cholinergic receptors. © 1994 Wiley-Liss, Inc.     

Passive-avoidance learning after medial septal lesions: Effect of experience and the peripheral sympathetic nervous system

Prior studies from our laboratory suggest that peripheral sympathetic ingrowth, which occurs in the hippocampus following medial septal lesions, is detrimental to the reaquisition of a spatial learning/memory task. To assess the generality of this finding we studied step-through passive-avoidance learning in animals with a medial septal lesion with or without superior cervical ganglionectomy under two experimental conditions. In the first condition, in which no prior experience with the task occurred, animals with a lesion demonstrated facilitation of learning. In the second condition, in which animals received pretraining with no shock prior to surgical manipulation, the behavior of animals with the lesion was similar to that of controls. No effect of ganglionectomy or initial sympathetic ingrowth was found in either condition. The results suggest that the effects of medial septal lesions on passive avoidance behavior are determined by the experimental condition and that early peripheral sympathetic ingrowth does not contribute either in a detrimental or beneficial fashion to passive avoidance learning.     

Failure of chronic physostigmine to ameliorate working memory deficits after medial septal lesions

To assess the potential usefulness of chronic acetylcholinesterase inhibition in the treatment of learning/memory disorders arising from central cholinergic deficient states, physostigmine was administered chronically to rats with medial septal lesions and the retention of a spatial/working memory task investigated. Three dose levels of physostigmine (0.025, 0.05, 0.075 mg/kg) were administered three times per day following medial septal lesions. Retention of a standard radial 8-arm maze task was assessed. Although the lesions transiently disrupted task performance, physostigmine therapy did not improve either daily performance or total recovery time. Our results suggest that chronic acetylcholinesterase inhibition is not effective in ameliorating the working memory deficits that occur after medial septal lesions.