Eyeblink conditioning depends critically on an identified brainstem-cerebellar circuit and is modulated under some circumstances by the hippocampus, amygdala, and other forebrain regions. Developmental studies of eyeblink conditioning could help elucidate questions concerning the behavioral expression of plasticity within these brain circuits and regions, and of their functional interactions, as they unfold during ontogeny. Recently, this laboratory has shown that conditioning of the eyeblink reflex develops dramatically between Postnatal Days (PND) 17 and PND 24 in the rat. The present study asked whether the developmental emergence of the eyeblink conditioned response (CR) occurs gradually or abruptly over this age range, and whether it reflects developmental changes in acquisition or expression of the learned eyeblink reflex. In Experiment 1, rat pups received two consecutive days of training beginning on PND 17, 20, or 24. Conditioned responses occurred at low levels on PND 17-18, intermediate levels on PND 20-21, and high levels on PND 24-25. In Experiment 2, 17-day-old rats received 2 days of training, 72 h apart, so that effects of training on PND 17 could be examined at an age, PND 20, when expression of the eyeblink CR was clearly possible. On PND 20, rat pups that had received paired training on PND 17 showed significantly faster conditioning than controls that had received unpaired training or no training on PND 17. These findings suggest that neural plasticity underlying associative learning developmentally precedes its overt expression in behavior. Hypotheses concerning the nature and locus of this learning are discussed.

Acoustic Stimulation↗

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Development of cholinergic neurons in rat brain regions: dose-dependent effects of propylthiouracil-induced hypothyroidism.

The effects of hypothyroidism on development of cholinergic system in brain regions (prefrontal cortex and hippocampus) were evaluated by measuring choline acetyltransferase (ChAT) activity and hemicholinium-3 binding to the high-affinity choline transporter. Various degrees of thyroid deficiency were produced by perinatal exposure to propylthiouracil (PTU) in drinking water ranging from 5 ppm (mg/l) to 25 ppm beginning at gestational day 18 until postnatal day 21. ChAT, a marker for cholinergic nerve terminals, was reduced by PTU in a dose-dependent manner. Concomitant with the enzyme deficits, hemicholinium-3 binding was elevated, suggesting an increase in neuronal impulse activity. Although similar changes were seen in both brain regions examined, the magnitude and duration of these changes were more definitive in the prefrontal cortex. Nonetheless, these neurochemical alterations appeared to be recoverable when the rats returned to a euthyroid state, and no further changes were observed as the animals reached adulthood. In comparison, data reported in a succeeding article indicate that deficits in cognitive function were first seen in weanling hypothyroid rats, but that the behavioral impairments lasted well into adulthood when thyroid status and cholinergic parameters in the brain appeared to have recovered to normal. These results suggest that alterations of cholinergic system caused by perinatal hypothyroidism are associated with neurobehavioral deficits at weaning, and these developmental deviations may cause permanent impairment of cognitive function despite recovery from the hormonal imbalance at adult ages.

Animals↗

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Radiolabeled platelet survival studies.

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Blood Platelets↗

PubMedDate not supplied

Use of a continuous-flow cell separator in density gradient isolation of lymphocytes.

A continuous-flow technique was developed to isolate and concentrate lymphocytes over Ficoll-Hypaque (FH) density gradients using an automated cell separator (Model CS-3000, Fenwal). Lymphocyte concentrates (LC) containing 6.51 X 10(9) mononuclear cells were obtained by standard leukapheresis techniques. Disposable apheresis kits were modified to allow the LC to be pumped into a separation chamber along with a counter-centrifugal flow of saline, removing the platelets and plasma by elutriation. The remaining cells were underlaid with 300 ml of FH, displacing the lymphocytes into a collection bag, where they were washed and concentrated. Mean leukocyte recovery was 59.2 percent (99.9% lymphocytes, n = 14). The final product contained 6.7 percent of the initial platelets and had a hematocrit of less than 1 percent. In paired studies using split leukocyte concentrates (n = 15), lymphocyte recovery obtained by the automated apheresis technique compared favorably with that obtained by standard manual FH gradients (59.8 +/- 3.4% versus 67.3 +/- 4.2%, p greater than 0.05) and platelet contamination was significantly reduced (2.7 +/- 0.5% versus 26.6 +/- 5.7% residual platelets, p less than 0.001). Equivalent lymphokine-activated killer (LAK) activity was generated from cells isolated by both manual and automated techniques. An automated continuous-flow cell separator can be used for rapid FH isolation of large numbers of lymphocytes, providing a sterile product suitable for human use.

Cell Separation↗

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Bulk cryopreservation of lymphocytes in glycerol.

The authors describe a method for freezing large amounts of peripheral blood lymphocytes (PBL) in a 20 percent glycerol solution. Between 0.6 and 4.3 X 10(9) cells in autologous plasma were frozen in polyethylene freezing bags in a final volume of 50 ml. The recovery after thawing averaged 89 +/- 14 percent with a mean viability by trypan blue dye exclusion of 80 +/- 7 percent (n = 11). In aliquots of fresh and frozen-thawed PBL from the same subjects radiolabeled with 111In, the radiolabeling efficiency for both fresh and thawed cells was 49 +/- 15 percent (p = 0.98, n = 5). The mitogen mean stimulation indices for glycerol-frozen cells (471 with phytohemagglutinin-M, 176 with pokeweed mitogen, and 380 with concanavalin A) were superior to those of cells frozen by a standard technique with dimethylsulfoxide (DMSO) (141, 47, and 123; p less than 0.05) and comparable to those of fresh PBL (403, 75, and 147). In a mixed lymphocyte culture, glycerol-frozen PBL showed significantly greater responsiveness to a pool of stimulator cells than did PBL frozen in DMSO (p = 0.03). Thawed cells are viable and functional as demonstrated by their response to mitogens and their ability to stimulate and respond in mixed lymphocyte culture.

Blood Preservation↗

PubMedDate not supplied

Viability of platelets following storage in the irradiated state. A pair-controlled study.

Gamma irradiation of blood products is a standard practice recommended for the prevention of posttransfusion graft-versus-host disease in susceptible hosts. We studied the effects of irradiation on stored platelet concentrates and evaluated whether platelets could be stored for 5 days in the irradiated state without adverse effects on their viability. Using a pair-controlled design in which each of six normal subjects acted as his or her own control, we compared in vitro storage characteristics and in vivo kinetics of platelet concentrates exposed to 30 Gy and stored for 5 days with those of platelet concentrates simply stored for 5 days without irradiation. Irradiation had no significant effects on in vitro storage characteristics (platelet count, mean platelet volume, pH, and white cell count) or on in vivo kinetics, including initial recovery and mean platelet survival. Using the multiple-hit model, initial recovery was 49.6 +/- 10.8 percent, and mean platelet survival was 5.6 +/- 1.05 days for irradiated concentrates, compared with 51.3 +/- 13.0 percent and 5.9 +/- 0.50 days, respectively, for the unirradiated control concentrates. We conclude that irradiation of platelet concentrates with up to 30 Gy has no effect on their in vivo recovery or survival, and that irradiation administered before storage of platelet concentrates does not interfere with their clinical efficacy.

Blood Platelets↗

PubMedDate not supplied

Efficacy of various methods of confidential unit exclusion in identifying potentially infectious blood donations.

To determine the efficacy of various methods of confidential unit exclusion (CUE) among donors at increased risk of HIV exposure, we surveyed AABB institutional members on their experience with 3 CUE methods: ballot or barcode, completed at the time of donation, and call-back, performed by the donor after leaving the donor center. From June 1985 to December 1987, 5,049,883 donations at 48 donor centers were evaluable for analysis. The results of this survey suggest that ballot and barcode methods of CUE are important adjuncts to other donor screening procedures in identifying potentially infectious units, and that both of these methods are superior to the call-back system of unit exclusion.

Blood Banking↗

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Assessment of physical function in aging rodents: a strategy for improving preclinical testing.

Geriatric medicine has recently focused on the biological mechanisms contributing to disability in the activities of daily living (ADLs), with special emphasis given to the study of sarcopenia, an age-related decline in muscle mass. Explaining the etiology of sarcopenia may provide useful information for the development of targeted interventions, especially those that are pharmacological in nature. However, exploratory studies aimed at evaluating the long-term effects of a particular intervention are costly and time consuming in a clinical setting. Therefore there is a need for preclinical testing of the efficacy of pharmacotherapies. This review provides (1) example of factors that contribute to the incidence of disability; (2) the conceptualization of a widely accepted human model of disability applied to an animal model; and (3) information on the potential advantages that may be realized from such translational research.

Activities of Daily Living↗

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Hypocapnia associated with cardiac stress scintigraphy in chest pain patients with panic disorder.

OBJECTIVE: Patients with recurrent chest pain but no evidence of coronary artery disease often meet diagnostic criteria for panic disorder (PD). However, it can be argued that the phenomenological diagnosis of PD may not be valid in these normal coronary chest pain (NCCP) patients. The purpose of this study is to additionally validate the diagnosis of PD in chest pain patients by comparing PCO2 levels before and during myocardial stress scintigraphy in those with and without PD. METHOD: End-tidal PCO2 was measured before and during myocardial stress scintigraphy in 22 patients being evaluated for chest pain. Psychiatric diagnoses were assessed by structured interview. RESULTS: Eleven of the 19 patients (58%) with negative scintigrams met DSM-III-R diagnostic criteria for current panic disorder. Prestress PCO2 levels were significantly lower in these patients. Eight of the nine NCCP patients with prestress PCO2 < 34 mm Hg had PD. CONCLUSIONS: The finding of stress-related hypocapnia associated with PD in NCCP patients provides additional support for the validity of the diagnosis of PD in this population. The potential value of PCO2 measurements in screening for PD in patients with chest pain merits additional study.

Aged↗

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Responses to laboratory psychosocial stress in postpartum women.

OBJECTIVE: Lactation has been associated with attenuated hormonal responses to exercise stress in humans. This study was designed to determine the effect of lactation on hypothalamic-pituitary-adrenal axis, autonomic nervous system, and anxiety responses to psychological stress. METHOD: The Trier Social Stress Test was administered to 24 lactating women, 13 postpartum nonlactating women, and 14 healthy control women in the early follicular phase of the menstrual cycle. Lactating women were stressed at least 40 minutes after last feeding their infant. RESULTS: ACTH, cortisol, heart rate, diastolic blood pressure, systolic blood pressure, and subjective anxiety ratings were all significantly increased in response to the psychological stress (all p <.0001). There were no differences among the three groups in any of these responses to the stress. However, postpartum nonlactating women did have a persistently higher systolic blood pressure and lower cardiac vagal tone than the lactating women and control subjects. In addition, the typical negative correlation between cardiac vagal tone and heart rate was consistently higher in lactating women than nonlactating postpartum women and controls, which suggests stronger vagal control of heart rate in lactating women. In addition, there was no change in oxytocin or allopregnanolone in response to the stress, and baseline oxytocin and allopregnanolone levels did not differ among the three groups. CONCLUSIONS: These results indicate that physiological and subjective responses to social stress are not attenuated in lactating women tested at least one hour after feeding their infant. However, enhanced vagal control of cardiac reactivity was observed in lactating women. In addition, postpartum women who did not lactate showed evidence of increased sympathetic and decreased parasympathetic nervous system tone.

Adult↗

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A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men.

This study describes sexual activity, nocturnal penile erections, and mood states as a function of serum levels of androgens in previously untreated hypogonadal men before and during hormone replacement, selected infertile men (elevated serum follicle-stimulating hormone levels), and normal men. Nocturnal penile tumescence and rigidity were measured with a portable monitor, and sexual activity and mood were assessed by prospective, self-reported written forms. Nocturnal erections were absent or of very low amplitude and duration in the untreated hypogonadal men compared to the infertile and normal men. Nocturnal erections increased steadily during hormone replacement and were in the normal range within 6 to 12 months of treatment. In contrast, serum testosterone concentration rapidly reached the upper range of normal. During treatment, the hypogonadal men reported increases in several aspects of sexual activity, including sexual interest and the number of spontaneous erections. On mood inventories, the untreated hypogonadal men scored significantly higher in ratings of depression, anger, fatigue, and confusion than did infertile and normal men. During hormonal replacement therapy these scores decreased, although the hypogonadal men continued to score higher in "depression" than did infertile and normal men. In most instances, the men with infertility and the normal men were statistically indistinguishable in nocturnal penile tumescence and rigidity parameters, self-reported sexual activity, and mood state. These data support the hypothesis that androgen treatment increases nocturnal and spontaneous erections, and sexual interest, and has some capacity to improve mood.

Adult↗