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Biomedical subjects

L J Grota

Publications and source records attributed to L J Grota.

At least 19 recordsLinked to original sources
PubMed1992

Decreased herpes simplex viral immunity and enhanced pathogenesis following stressor administration in mice.

Mild electric footshock stress was delivered during the dark portion of a 12:12 h light:dark cycle to C57BL/6 female mice that were infected with herpes simplex virus-type 1 (HSV). The studies were designed to correlate viral titer with both humoral and cell-mediated immune responses to HSV infection. Footshock was observed to result in decreased HSV-specific immunity. The numbers of leukocytes in spleens and draining popliteal lymph nodes of footshocked mice were depressed compared to both apparatus control and home cage control mice. A significant suppression of the HSV-specific cytotoxic T lymphocyte (CTL) response was observed in both the spleen and popliteal lymph nodes of footshocked mice. Serum IgM anti-HSV antibody titers were also depressed in footshocked mice. These changes were shown to be correlated with significantly increased viral titers in footshocked mice compared to control mice. These data demonstrate that administration of a relatively mild stressor is associated with depressed HSV-specific cellular and humoral immunity and is associated with increased pathogenicity.

Animals↗
PubMed1990

Voluntary consumption of cyclophosphamide by nondeprived Mrl-lpr/lpr and Mrl +/+ mice.

Cyclophosphamide dissolved in several dilutions of chocolate milk was presented for 20 hr daily to nondeprived, symptomatic, autoimmune Mrl-lpr/lpr and asymptomatic Mrl +/+ mice. In the absence of cyclophosphamide, daily consumption was inversely related to the concentration of the chocolate milk solutions and increased from the first to the fourth day of exposure. There were no effects of strain or sex on the consumption of plain chocolate milk. Consumption of 0.1 or 0.2 mg cyclophosphamide per ml of different dilutions of chocolate milk increased over days 1-4 and decreased on day 8. Consumption of 0.4 mg/ml cyclophosphamide did not change over days. Generally, consumption was inversely related to the cyclophosphamide concentration. Females consumed more cyclophosphamide than males. Autoimmune lpr/lpr mice consumed more cyclophosphamide than +/+ mice. Dilution of chocolate milk had no effect on consumption of cyclophosphamide. Lymphoproliferation and anti-ssDNA antibody titer were reduced by the consumption of cyclophosphamide-chocolate milk solutions. It is hypothesized that autoimmune lpr/lpr mice voluntarily consume more cyclophosphamide than asymptomatic +/+ mice in an effort to "correct" their immune system dysregulation.

Animals↗
PubMed1990

The effects of stress on the development of immunological memory following low-dose antigen priming in mice.

Observable stress effects on immune responses may be a function of the quantitative and qualitative characteristics of the stressor, and the outcome measurement of immunity. Further, the effects of stress on humoral immunity, in particular, may be sensitive to the concentrations of antigen used to elicit a response. We have studied the effects of footshock stress during the time of priming with low concentrations of antigen on the secondary response to another low dose of antigen. The secondary humoral immune response of C3H/HeJ mice to the protein antigen keyhole limpet hemocyanin was examined following footshock, exposure to the apparatus without shock, or exposure to the home cage. Footshock reproducibly depressed the IgG anti-KLH response, and the effect on the IgM response was sporadic. Initially, footshock was administered for 7 days before and 7 days after priming with low amounts of antigen. Subsequent studies demonstrated that a single footshock session delivered 24 h after priming could suppress the IgG anti-KLH response.

Animals↗
PubMed1989

Phototherapy for seasonal major depressive disorder: effectiveness of bright light of high or low intensity.

Eleven females and five males with fall/winter seasonal affective disorder were randomly assigned to 7-day treatment regimens from 8 p.m. to 10 p.m. using identical light at 2000 or 300 lux. A modified Hamilton Rating Scale for Depression and a Beck Depression Inventory were administered before treatment, after treatment # 7, and 2 weeks after phototherapy was terminated. Analysis of variance with repeated measures revealed a significant interaction between sex of the patient, intensity of the lights, and day of rating for scores on both the modified Hamilton Rating Scale for Depression and the Beck Depression Inventory. For both measures, the interaction occurred because all groups showed a decrease in depression ratings during the phototherapy exposure period, but only females at the higher intensity continued to have low depression scores 2 weeks after light treatment had stopped. These data indicate that bright light at both high (2000 lux) and low (300 lux) intensities is able to reduce depression in patients with seasonal affective disorder. The data also indicate that both sex of the patient and intensity of the light may interact to determine the latency to relapse.

Adult↗
PubMed1989

Voluntary consumption of cyclophosphamide by Mrl mice.

Fluid-deprived, lupus-prone Mrl-lpr/lpr and congenic Mrl +/+ mice were provided with a single drinking bottle containing varying concentrations of cyclophosphamide (CY) dissolved in chocolate milk. Eighteen- and 20-week-old Mrl-lpr/lpr males with manifest symptoms of autoimmune disease voluntarily consumed more of the CY solution than Mrl +/+ mice of the same age after 1 week of 1 hr/day exposures. The volume of CY-laced chocolate milk consumed was sufficient to attenuate lymphadenopathy and the elevated anti-DNA antibody titers in these animals. When testing began before the development of manifest symptoms of autoimmune disease, there were no differences between the two substrains. These results are consistent with the hypothesis that behavioral processes can act to correct homeostatic imbalances within the immune system.

Animals↗
PubMed1988

Analgesia induced by N-acetylserotonin in the central nervous system.

The relationship between N-acetylserotonin (NAS) in the central nervous system (CNS) and responses to pain was investigated. Using the rat tail-flick model, we initially replicated the work of others showing that intraventricular (IVC) injection of a dipeptide structurally similar to both NAS and serotonin was capable of inducing analgesia in the rat. We then showed that IVC-NAS, but not serotonin elicited analgesia in much the same manner as the dipeptide. This effect proved to be very specific as it required the presence of both an acetyl group on the terminal side chain amine as well as a hydroxyl group on the C-5 position of the indole ring. Substitution of the C-5 hydroxyl by a methoxyl group (melatonin) abolished the analgesic effect. Similarly, removing the N-acetyl substitution (serotonin) also eliminated the analgesia. IVC injection of highly specific antiserum to NAS induced hyperalgesia. Furthermore, an interaction was found between NAS and opiate systems. We demonstrated that while naloxone, the opiate antagonist, has no hyperalgesic properties of itself, it did counteract the analgesia induced by NAS. Similarly, NAS antiserum reversed the analgesia induced by the opiate morphine. This work provides evidence that NAS is an endogenously active substance within the CNS pain network.

Analgesia↗
PubMed1987

Taste aversion learning in autoimmune Mrl-lpr/lpr and Mrl +/+ mice.

Conditioned taste aversion to a neutral stimulus paired with an immunosuppressive drug (cyclophosphamide) was assessed in lupus-prone MRL-lpr/lpr and congenic control (MRL +/+) mice. The presence of lymphoproliferation in MRL-lpr/lpr mice was associated with poorer taste aversion learning and varied as a function of the dose of cyclophosphamide. There were no differences in learning performance between MRL-lpr/lpr and MRL +/+ mice when the animals were tested at an age prior to the development of lymphadenopathy, or when lithium chloride or electric shock were used as unconditioned stimuli. These results are consistent with the hypothesis that the immune status of an organism has an impact on behavior and the possibility that behavior can serve an in vivo immunoregulatory function.

Animals↗
PubMed1986

Effects of bright incandescent light on seasonal and nonseasonal major depressive disorder.

Previous research has indicated that exposure to bright fluorescent light can benefit clinically depressed individuals. The present study, a 1- to 2-week open trial of bright (greater than or equal to 2,000 lux) incandescent light with seasonal (fall/winter) and nonseasonal depressives, produced a therapeutic effect on seasonal depression, as measured by three criteria for recovery: final score on the Hamilton Rating Scale for Depression (HRSD) less than 10; final HRSD score less than or equal to 50% of pretreatment HRSD score; no longer meets DSM-III criteria for major depressive disorder. Phototherapy was not effective in the nonseasonal patients, whose functioning was more impaired than that of the seasonal subjects even before the trial. No adverse effects were observed in any patient.

Adult↗
PubMed1985

Melatonin and N-acetylserotonin stress responses: effects of type of stimulation and housing conditions.

The effects of housing condition and type of stimulation on serum melatonin and N-acetylserotonin (NAS) were investigated. Male rats were housed under a 12/12-hour light-dark cycle, with ad libitum food and water, either individually or in groups of four. At the start of the light phase, separate groups were sacrificed at rest or subjected for 3 minutes to the stimulation of cold water, noise, novel environment, or ether vapour and then decapitated at 0, 5, 15, 30 or 60 minutes after the end of stimulation. Melatonin was measured by a modified radioimmunoassay and NAS by a specific radioimmunoassay. Melatonin levels responded to stimulation with an increase, while NAS levels responded with a decrease. Housing condition had no effect on hormone response. However, the pattern of response for each of the two hormones differed greatly among the stimuli. For melatonin, cold water was the most potent stimulus, followed by noise, novel environment, and ether. NAS responded most to ether, fleetingly to cold, and in a bimodal manner to noise. The data are interpreted as suggesting that separate mechanisms regulate serum melatonin and serum NAS is response to environmental stimulation and that under appropriate control conditions melatonin from the pineal is very responsive to environmental stimuli, in a manner similar to that of pituitary hormones.

Animals↗
PubMed1985

Immunohistochemical assessment of melatonin binding in the pineal gland.

Melatonin binding in the pineal gland of albino rats is estimated using an immunohistochemical procedure. Binding is saturable, has relatively high affinity (Apparent KD = 2.7 nM), and competition studies indicate binding of indoleamines possessing an N-acetyl group on the terminus of the side chain (N-acetylserotonin and melatonin). These data are consistent with the interpretation that immunohistochemically determined melatonin in unfixed pineal tissue is assessing binding of N-acetylated indolealkylamines to pineal cell components. In albino rats maintained on 12-hour light: 12-hour dark cycles, melatonin binding exhibits a diurnal rhythm with low levels of saturation (30%) early in the light and saturation by endogenous melatonin near the onset of darkness. An annual rhythm of melatonin binding was observed in albino rats with low levels during the summer and high levels during the winter. Other rats were maintained on 12-hour light:dark cycles and fed for 2 hours either early in the light period or early in the dark period. For both morning- and evening-fed animals, melatonin binding was high prior to feeding and dropped immediately after feeding. Changes in melatonin binding that occur in response to alterations of feeding and time of year suggest the possibility that this binding reflects a functional site for melatonin.

Animals↗
PubMed1985

Serum melatonin response to melatonin administration in the Syrian hamster.

Chronic daily administration of melatonin (MT) can have potent effects on reproduction in the hamster. Various theories have been elaborated to explain these effects but little information has been available on circulating levels of MT following MT administration. We have examined the serum MT response in the male hamster to a single dose of 25 micrograms MT administered in the morning or in the afternoon--the same timing and dose used by others to produce reproductive effects. With both morning and afternoon administration, serum MT increased above 1,000 pg/ml and remained above the highest basal levels during most of the 24-hour cycle. These levels are clearly supraphysiologic ones. The decline in serum MT showed two distinct components following morning administration. Half-life of the initial component which probably represents rapid distribution into tissues was 17.3 min. A half-life of 25.1 h was calculated for the second component. We conclude that use of a 25-micrograms dose of melatonin to study pineal effects may be misleading.

Animals↗
PubMed1985

Scheduled feeding and 24-hour rhythms of N-acetylserotonin and melatonin in rats.

Male rats, kept under a lighting condition of 14-h light, 10-h dark, were subjected to scheduled feeding regimens. Food was available either in the early light phase or the early dark phase. The 24-h rhythms of serum corticosterone and of N-acetylserotonin (NAS) and melatonin (MT) in the pineal and serum were determined. It was found that whereas serum corticosterone and NAS rhythms responded to the feeding schedules, the rhythms of pineal NAS and of serum and pineal MT remained synchronized with the light-dark cycle. These findings indicated that the pineal was not the major source of circulating NAS. Whereas environmental lighting was the dominant "Zeitgeber" for the NAS rhythms in the pineal and the MT rhythms in the pineal and serum, for serum NAS rhythm, food presentation was the stronger Zeitgeber.

Animals↗
PubMed1979

Plasma corticosterone response to serotonin altering drugs in the 3-day-old rat.

Three-day-old rats were injected with various neurotransmitter altering agents to demonstrate a functional relationship between these drugs and plasma corticoid levels. Plasma corticosterone levels were increased after injection of methiothepin, methysergide, and 5-hydroxytryptophan (5-HTP), but were not changed by cholinergic, adrenergic, and dopaminergic compounds. Imipramine alone had no effects on plasma corticoids but in combination with 5-HTP resulted in a more sustained response than 5-HTP alone. Afunctional relationship between plasma corticosterone and serotonin receptors has been demonstrated in the 3-day-old rat. The presence of this relationship just after birth suggests the possibility that serotonin may be a mediator of early experience effects on later adrenocortical function.

5-Hydroxytryptophan↗