Increased ipsilateral expression of Fos following lateral hypothalamic self-stimulation

Immunohistochemical labeling of Fos protein was used to visualize neurons activated by rewarding stimulation of the lateral hypothalamic level of the medial forebrain bundle (MFB). Following training and stabilization of performance, seven rats were allowed to self-stimulate for 1 h prior to anesthesia and perfusion. Brains were then processed for immunohistochemistry. Two control subjects were trained and tested in an identical manner except that the stimulator was disconnected during the final 1 h test. Among the structures showing a greater density of labeled neurons on the stimulated side of the brains of the experimental subjects were the septum, lateral preoptic area (LPO), medial preoptic area, bed nucleus of the stria terminalis, substantia innominata (SI), and the lateral hypothalamus (LH). Several of these structures, the LPO, SI, and LH, have been implicated in MFB self-stimulation by the results of psychophysical, electrophysiological, and lesion studies.     

Gene transfer to vein graft wall by HVJ-liposome method: time course and localization of gene expression

BACKGROUND: A novel gene transfer method using liposomes with a viral envelope of hemagglutinating virus of Japan (HVJ) has been reported to be very effective for gene transfection into somatic cells and might be applicable to improve the patency of vein grafts. The present study examined the time course and localization of gene expression to assess the feasibility of ex vivo gene transfer into the vein graft by the HVJ-liposome method. METHODS: The HVJ-liposome complex containing either beta-galactosidase plasmid DNA (deoxyribonucleic acid) or no genes (controls) (experiment 1) or fluorescein isothiocyanate-labeled oligonucleotides either with or without HVJ-liposomes (experiment 2) was infused into rabbit vein grafts and allowed to incubate before autologous transplantation to carotid arteries. RESULTS: In experiment 1, all grafts incubated with beta-galactosidase plasmid with HVJ-liposomes showed the blue staining of X-gal 7 days after operation, whereas the controls did not. The blue granules were present in the medial and adventitial tissue and were still present after 14 days. In experiment 2, many fluorescein isothiocyanate-labeled nuclei were observed in the graft wall 2 and 4 days after operation and remained present mainly in the media of HVJ-liposome-treated grafts after 7 and 14 days, when no fluorescein isothiocyanate activity was observed without HVJ-liposome treatment. CONCLUSIONS: These results demonstrated the feasibility of ex vivo transfection to the medial and adventitial tissue of the vein graft by the HVJ-liposome method and suggest the possibility of its clinical application to prevent vein graft failure.     

Long-term alterations in growth factor mRNA expression following seizures

Pneumocystis carinii pneumonia (PCP) is one of the most predominant opportunistic infectious diseases in patients with AIDS. Nested PCR has been described as a sensitive and specific tool for detecting P. carinii DNA in clinical specimens. Little is known about the correlation of positive PCR results and clinical evidence of PCP in patients with different forms of immunosuppression. One hundred and thirty-six sputum samples, 26 tracheal-bronchial aspirate samples, 35 bronchoalveolar lavage samples, and 11 lung biopsy samples from (i) human immunodeficiency virus (HIV)-infected patients with AIDS, (ii) immunocompromised patients with leukemia or lymphoma, and (iii) immunocompetent control patients were investigated by a nested PCR amplifying DNA from the mitochondrial large subunit of P. carinii. All patients suffered from acute episodes of respiratory disease. The resulting data were correlated with clinical evidence of PCP. A high degree of association of positive P. carinii PCR results and clinical evidence of PCP in HIV-infected patients with AIDS was found. When calculated for bronchoalveolar lavage and lung biopsy samples, the positive and the negative predictive values of P. carinii PCR for PCP diagnosis in HIV-infected patients with AIDS were 1 and the specificity and the sensitivity were 100%. In contrast, in the group of patients with leukemia or lymphoma, the positive predictive value of the nested PCR for these materials was found to be as low as 0.09, the negative predictive value was 0.73, the specificity was 44.4%, and the sensitivity was 25.0%. No P. carinii DNA could be detected in specimens from immunocompetent patients. In summary, in contrast to patients with leukemia and lymphoma, nested PCR seems to be a sensitive and specific tool for PCP diagnosis in HIV-infected patients with AIDS.     

Conditioned Fos expression following morphine-paired contextual cue exposure is environment specific.

Environmental cues associated with drug administration elicit neural activation in circuits involved in cognitive processes and emotional regulation. An important question is whether the neural activation observed is specific to the drug-paired environment or is due to a generalized activation induced by previous drug treatment or changes in arousal state. Rats were treated with morphine (5 mg/kg ip) in one environment and saline in an alternative environment, and their brains were later examined for conditioned Fos expression after placement in one of these environments without drug administration. Increases in neural activation after drug-paired environmental exposure were dependent on exposure to the specifically paired environment; exposure to an alternative environment in morphine-treated rats did not elicit similar increases in Fos expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fos expression in rat pontine tegmental neurons following activation of the medial preoptic area

Because murine myeloma plasma cells and normal human lymph node plasma cells express BCL-X, we evaluated BCL-X expression in malignant human plasma cells. BCL-X expression was detected in several human myeloma cell lines, as well as in CD38-sorted bone marrow cells obtained from some patients. Only the antiapoptotic long form of BCL-X (BCL-X-L), was detected. Because BCL-X-L expression can protect tumor cells from apoptotic death induced by chemotherapeutic agents, we tested the clinical relevance of expression in 55 archival bone marrow biopsies. The biopsies were stained by immunohistochemistry, and BCL-X expression was correlated with the subsequent response to treatment. BCL-X expression in malignant plasma cells strongly correlated with decreased response rates in patient groups treated with either melphalan and prednisone or vincristine, Adriamycin, and dexamethasone. Response rates were 83-87% in non-BCL-X-expressing cases and 20-31% in BCL-X-expressing cases. In addition, BCL-X expression was more frequent in specimens taken from patients at relapse (77%), when compared to those at initial diagnosis (29%). Further support for the association of drug resistance with BCL-X-L expression came from studies of the 8226 dox-40 cell line. This line, which expresses p-glycoprotein and serves as a model of multidrug resistance in multiple myeloma cells, demonstrated an up-regulated expression of BCL-X-L, which was relatively specific, in that BCL-2 or BAX expression was not altered. In addition, dox-40 cells demonstrated a generalized resistance to apoptosis that was induced by several different agents. These results indicate that malignant plasma cells can express BCL-X-L and that such expression may be a marker of chemoresistant disease.     

The time course of pulmonary transfer factor changes following heart transplantation

OBJECTIVE: The pulmonary transfer factor for carbon monoxide (TLCO) has been reported to decline following heart transplantation, but the time course of this decline is not well documented. The aim of this study was to define the longitudinal changes in TLCO after heart transplantation. METHODS: Single breath TLCO, lung volumes and expiratory flow rates were prospectively measured in 57 patients (mean age 49 years, range 19-61) before and at least once after heart transplantation. Thirty seven of the 57 patients had four post-transplant assessment which were performed at 6 weeks, 3, 6 and 12 months in 26 patients and at 12, 18, 24 and 36 months in 11 patients. Results were compared with data from 28 normal subjects (mean age 40 years, range 19-61). RESULTS: Before transplantation there was a mild impairment of lung volumes and expiratory flow rates. At 6 weeks after transplantation, there was a further reduction in the forced expiratory volume in one second, forced vital capacity, residual volume and total lung capacity, but all of these increased in the subsequent measurements to exceed their pre-transplant values at about 1 year after transplantation. Haemoglobin-corrected TLCO was also reduced before transplantation compared to normal controls (74.3% and 98.6% of predicted respectively, P < 0.001). Although TLCO per unit alveolar volume (KCO) was relatively preserved in heart transplant candidates, it was still significantly lower than that of normal controls (92.6% and 105.3% of predicted respectively, P < 0.05). After transplantation, mean haemoglobin-corrected TLCO and KCO declined by 12% and 20% of predicted respectively) with the majority of patients having reductions greater than 10% of predicted. The decline in TLCO and KCO was evident at 6 weeks after transplantation with no further changes in the subsequent measurements. CONCLUSIONS: TLCO is reduced in heart transplant candidates and declines further after heart transplantation despite improvement in lung volumes and airway function. The early and non-progressive nature of TLCO decline suggests an aetiology exerting its effect on TLCO within the first 6 weeks after transplantation.     

Fos expression in the prefrontal cortex and nucleus accumbens following exposure to retrospective timing tasks.

The dorsal striatum and prefrontal cortex have been implicated in interval timing. We examined whether performance of temporal discrimination tasks is associated with increased neuronal activation in these areas, as revealed by Fos expression, a marker for neuronal activation. In Experiment 1, rats were trained on a discrete-trials temporal discrimination task in which a light (22 cd/m2) was presented for a variable time, t (2.5–47.5 s), after which levers A and B were presented. A response on lever A was reinforced if t t > 25 s. A second group was trained on a light-intensity discrimination procedure, in which a light of variable intensity, i (3.6–128.5 cd/m2) was presented for 25 s. A response on lever A was reinforced if i i > 22 cd/m2. In Experiment 2, bisection procedures were used to assess temporal (200–800 ms, 22 cd/m2) and light-intensity (3.6–128.5 cd/m2, 400 ms) discrimination. The increase in proportional choice of lever B as a function of stimulus duration or intensity conformed to a two-parameter logistic equation. Fos expression in the prefrontal cortex and nucleus accumbens was higher in rats performing temporal discrimination tasks than in those performing light-intensity discrimination tasks, indicating greater neuronal activation in these areas during temporal discrimination tasks. Fos expression in the dorsal striatum did not differ between rats performing temporal and light-intensity discrimination tasks. These results suggest that the prefrontal cortex and nucleus accumbens are involved in temporal discrimination. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The time course for elevated muscle protein synthesis following heavy resistance exercise

It has been shown that muscle protein synthetic rate (MPS) is elevated in humans by 50% at 4 hrs following a bout of heavy resistance training, and by 109% at 24 hrs following training. This study further examined the time course for elevated muscle protein synthesis by examining its rate at 36 hrs following a training session. Six healthy young men performed 12 sets of 6- to 12-RM elbow flexion exercises with one arm while the opposite arm served as a control. MPS was calculated from the in vivo rate of incorporation of L-[1,2-13C2] leucine into biceps brachii of both arms using the primed constant infusion technique over 11 hrs. At an average time of 36 hrs postexercise, MPS in the exercised arm had returned to within 14% of the control arm value, the difference being nonsignificant. It is concluded that following a bout of heavy resistance training, MPS increases rapidly, is more than double at 24 hrs, and thereafter declines rapidly so that at 36 hrs it has almost returned to baseline.     

Inflammation-induced Fos protein expression in the rat spinal cord is enhanced following dorsolateral or ventrolateral funiculus lesions

Previous studies have shown an enhanced expression of Fos protein-like immunoreactivity in the lumbar spinal cord of rats with complete spinal transection following persistent hindpaw inflammation. To further locate the spinal pathways responsible for these effects, we compared the inflammation-evoked Fos expression in rats with bilateral lesions of the dorsolateral (DLFX) or ventrolateral (VLFX) funiculus, and with rats with a sham operation. The results indicate that the number of Fos-labeled neurons was significantly increased in all laminae of the dorsal horn ipsilateral to the inflamed hindpaw and in contralateral deep dorsal horn in both DLFX and VLFX rats compared to sham-operated rats. Moreover, when comparing DLFX and VLFX rats, in the ipsilateral spinal cord, DLFX resulted in more Fos expression in the deep dorsal horn; in contrast, a larger number of Fos-labeled cells in superficial laminae was observed in VLFX rats. These results suggest that modulatory systems, which descend in both DLF and VLF pathways, mediate the enhanced net descending nociceptive inhibition after persistent inflammation, although the supraspinal sites of origin of each pathway are likely functionally diverse.     

Lipopolysaccharide-induced Fos expression in hypothalamic nuclei of neonatal rats

The inability of neonates to fully evoke the acute-phase reaction to infection is thought to be due in part to central nervous system immaturity. We used the expression of Fos protein to evaluate whether acute-phase reaction deficits in neonates may indeed be linked to unresponsiveness of brain regions that mediate the responses to infection in adult animals. In this study, we used lipopolysaccharide (LPS) as the infectious agent. Rats aged 0-1, 3, 6, 9, 12 and 15 days were divided into groups treated with low- or high-dose LPS (Escherichia coli; 50 and 500 micrograms/kg, respectively, i.p.) or pyrogen-free saline (PFS) i.p. Two hours after injection, the animals were deeply anesthetized, sacrificed, and their brains removed for Fos immunocytochemistry. Fos-like immunoreactive (FLI) neurons in the preoptic area (POA), paraventricular nucleus of the hypothalamus (PVN), and organum vasculosum laminae terminalis (OVLT) were compared between the treatment and the age groups. The forebrain was devoid of FLI neurons in 1-day-old rats, but FLI neurons were present at 3 days of age and continued to increase with age until 9 days after birth. There were no significant differences between the LPS- and PFS-treated groups until day 12 of age. At 12 and 15 days of age, FLI neurons in the PVN, medial preoptic and lateral preoptic nuclei, and the area surrounding the OVLT were greater in the LPS-treated animals. The expression appeared to be both age- and dose-dependent. These observations show that the rat brain structures that participate in the mediation of the acute-phase reaction do not become responsive to systemic pyrogens until 12 days of age, thus suggesting that insensitivity of the brain to pyrogenic agents may be partly responsible for the poor response of neonates to infectious agents.     

Prolonged expression of zinc finger immediate-early gene mRNAs and decreased protein synthesis following kainic acid induced seizures

STUDY DESIGN: A high-resolution strain measurement technique was applied to axially loaded parasagittal sections from thoracic spinal segments. OBJECTIVES: To establish a new experimental technique, develop data analysis procedures, characterize intrasample shear strain distributions, and measure intersample variability within a group of morphologically diverse samples. SUMMARY OF BACKGROUND DATA: Compression of intact vertebral bodies yields structural stiffness and strength, but not strain patterns within the trabecular bone. Finite element models yield trabecular strains but require uncertain boundary conditions and material properties. METHODS: Six spinal segments (T8-T10) were sliced in parasagittal sections 6-mm thick. Axial compression was applied in 25-N increments up to sample failure, then the load was removed. Contact radiographs of the samples were made at each loading level. Strain distributions within the central vertebral body were measured from the contact radiographs by an image correlation procedure. RESULTS: Intrasample shear strain probability distributions were log-normal at all load levels. Shear strains were concentrated directly inferior to the superior end-plate and adjacent to the anterior cortex, in regions where fractures are commonly seen clinically. Load removal restored overall sample shape, but measurable residual strains remained. CONCLUSIONS: This experimental model is a suitable means of studying low-energy vertebral fractures. The methods of data interpretation are consistent and reliable, and strain patterns correlate with clinical fracture patterns. Quantification of intersample variability provides guidelines for the design of future experiments, and the strain patterns form a basis for validation of finite element models. The results imply that strain uniformity is an important criterion in assessing risk of vertebral failure.     

Expression of Fos in the rat forebrain following experimental tooth movement

Orthodontic tooth movement is known to cause pain and discomfort to patients. Mechanically induced inflammatory responses in the periodontium are assumed to be related to the mechanism of pain sensation. An immediate-early gene, c-fos, that is expressed within some neurons following synaptic activation, is widely used as a marker for neuronal activity following noxious or innocuous stimulation. We have recently demonstrated that experimental tooth movement produced Fos induction in the ipsilateral trigeminal subnucleus caudalis and in the bilateral lateral parabrachial nucleus, which is known to be involved in the transmission of nociceptive information. As a further step, we investigated the distribution of Fos-like immunoreactive neurons in the upper brain regions. Twenty-four hours after the commencement of the experimental tooth movement, the Fos-like immunoreactive neurons appeared in the central nucleus of the amygdala (Ce), paraventricular nucleus of the hypothalamus (PVH), and paraventricular nucleus of the thalamus (PV) of the experimental rats. The numbers of the labeled neurons were significantly increased by 639% (P < 0.001) and 644% (P < 0.001) in the ipsilateral and contralateral sides of the Ce, respectively, by 292% (P < 0.001) and 307% (P < 0.001) in the ipsilateral and contralateral sides of the PVH, and by 264% (P < 0.0001) in the PV with respect to sham control rats. These results suggest that nociceptive information caused by experimental tooth movement might be transmitted and modulated in several regions of the forebrain.     

The time course of categorization.

The extended generalized context model (EGCM) is presented as a formal model of the time course of categorization of complex stimuli. The model explains the effects of time constraints on categorization. The EGCM accurately accounts for existing data on categorization under time pressure. The model was tested further in 2 experiments. In both experiments, processing time in a perceptual categorization task was restricted by unpredictable peremptory response signals. In Experiment 1, restrictions of processing time had systematic effects on response proportions, and these effects were well explained by the EGCM. Experiment 2 showed that perceptual salience and utility have independent effects on the time course of categorization, as predicted by the EGCM. The EGCM's relation to other models of the time course of categorization is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treadmill running induces striatal Fos expression via NMDA glutamate and dopamine receptors

Several non-physiological stimuli (i.e. pharmacological or electrical stimuli) have been shown to induce Fos expression in striatal neurons. In this work, striatal Fos (i.e. Fos-like) expression was studied after physiological stimulation, i.e. motor activity (treadmill running at 36 m/min for 20 min). In rats killed 2 h after the treadmill session, Fos expression was observed in the medial region of the rostral and central striatum, and in the dorsal region of the caudal striatum. Fos expression was prevented by pretreatment with the non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (0.1 mg/kg) or the D1 dopamine receptor antagonist SCH-23390 (0.1 mg/kg), but not by pretreatment with the D2 receptor antagonist eticlopride (0.5 mg/kg). Thirty-six hours after 6-hydroxydopamine lesion, a considerable reduction in treadmill-induced Fos expression was observed in both sides; however, Fos expression in the lesioned striatum was higher than in the contralateral intact striatum. Several weeks after unilateral 6-hydroxydopamine lesion of the nigrostriatal system, treadmill-induced Fos expression was significantly, but not totally, reduced in the lesioned striatum. Corticostriatal deafferentation also led to considerable reduction in treadmill-induced Fos expression. The present results indicate that exercise induces striatal Fos expression and that, under physiological stimulation, concurrent activation of D1 and NMDA receptors is necessary for such expression to occur. Reduction of Fos expression is practically absolute after acute blockage of these receptors, but not after lesions, possibly due partially to compensatory changes.     

The time course and significance of cannabis withdrawal.

Withdrawal symptoms following cessation of heavy cannabis (marijuana) use have been reported, yet their time course and clinical importance have not been established. A 50-day outpatient study assessed 18 marijuana users during a 5-day smoking-as-usual phase followed by a 45-day abstinence phase. Parallel assessment of 12 ex-users was obtained. A withdrawal pattern was observed for aggression, anger, anxiety, decreased appetite, decreased body weight, irritability, restlessness, shakiness, sleep problems, and stomach pain. Onset typically occurred between Days 1-3, peak effects between Days 2-6, and most effects lasted 4-14 days. The magnitude and time course of these effects appeared comparable to tobacco and other withdrawal syndromes. These effects likely contribute to the development of dependence and difficulty stopping use. Criteria for cannabis withdrawal are proposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)