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PubMed1995

Cellular basis of temporal synaptic signalling: an in vitro electrophysiological study in rat auditory thalamus.

1. The cellular mechanisms underlying temporal synaptic signalling of tectothalamic pathways were investigated in rat medial geniculate body (MGB) maintained in vitro. Stimulation of the brachium of the inferior colliculus elicited either a short latency, single- (or dual-) spike or a long latency (10-80 ms) burst in MGB neurones. The delayed burst response was found in most non-lemniscal or caudodorsal MGB (MGd) neurones, whereas single-spike units were mainly seen in the lemniscal ventral MGB (MGv). Population latency analysis revealed that the overall relay time of tectothalamic transmission is approximately 50 ms, with at least two excitation peaks occurring around 8 and 15 ms, respectively. 2. Intracellular recordings showed that the delayed burst responses in MGd neurones were mediated by an EPSP-triggered low threshold spike (LTS). Small variations in either the membrane voltage or in EPSP amplitude induced significant shifts of LTS latency. 3. Compared with MGv cells, MGd neurones exhibited a more negative resting membrane potential and a prolonged EPSP; they lacked an apparent hyperpolarization-activated inward rectifier (Ih). These factors seem to lead collectively to a dominant occurrence of long latency burst response in the MGd. In the majority of single-spiking MGv cells that expressed a clear Ih, application of Cs+ consistently hyperpolarized the cell, which transformed a single-spike synaptic response into an EPSP-LTS burst or a subthreshold EPSP. 4. Taken together, these data suggest that the monosynaptic tectothalamic pathways are capable of introducing a ventrodorsal gradient in auditory response time. This synaptic activity pattern is probably dominantly regulated by a set of membrane conductances expressed endogenously in thalamocortical neurones.

Animals↗
PubMedDate not supplied

Regulation of cell volume and intracellular pH in hyposmotically swollen rat osteosarcoma cells.

The maintenance of cell volume involves transduction of a volume-sensing signal into effectors of volume-regulatory transporters. After exposure to anisotonic conditions, cells undergo compensatory volume changes that are mediated by active transport and passive movement of ions and solutes. Intracellular pH (pHi) homeostasis may be compromised during these processes. We have studied pHi and some of the signal transduction mechanisms involved in the regulatory volume decrease (RVD) that occurs after exposure to hypoosmolar conditions in rat osteosarcoma cells, ROS 17/2.8. Cells were loaded with BCECF; pHi and cell volume were estimated by dual excitation ratio fluorimetry. Swelling of cells in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffered hypotonic medium induced a rapid cell swelling followed by an incomplete RVD of approximately 30% in suspended (i.e., round) cells and approximately 60% in attached (i.e., spread) cells that was independent of subpassage number. RVD was inhibited by ouabain, valinomycin, and high external [K+], all of which should reduce the cell membrane electrochemical gradient for K+. Inhibition of RVD was induced also by decreasing intracellular [Ca2+] with BAPTA-AM and by depletion of Cl-, indicating the role of calcium-regulated K+ and Cl- efflux during RVD. Depolymerization of actin filaments by cytochalasin D prolonged the RVD three-fold and nonspecific activation of GTP-binding proteins up-regulated RVD. In attached cells the hypoosmolar-induced swelling caused a large reduction in pHi (approximately 0.7 units), which was sustained as long as cells were in hypoosmotic medium. The reduction of pHi induced by cell swelling was inhibited by Na(+)-free extracellular medium, ouabain, the tyrosine kinase inhibitor genistein, and to a lesser extent by Cl(-)-free medium. However, amiloride failed to inhibit the hypoosmolar-induced reduction of pHi. Collectively these data indicate that RVD of ROS 17/2.8 cells in HEPES-buffered medium is dependent on conductive efflux of K+ and Cl- that is regulated by cell shape, actin, and GTP-binding proteins. The sustained inhibition of pHi homeostasis induced by cell swelling may reflect the existence of cell volume sensing mechanisms that operate through tyrosine kinases to regulate pHi.

Actins↗
PubMed2005

Substance use disorders in individuals with body dysmorphic disorder.

BACKGROUND: Little is known about substance use disorders (SUDs) in individuals with body dysmorphic disorder (BDD). Although studies have examined SUD comorbidity in BDD, no previous studies have examined clinical correlates of SUD comorbidity. METHOD: We examined rates and clinical correlates of comorbid SUDs in 176 consecutive subjects with DSM-IV BDD (71% female; mean +/- SD age = 32.5 +/- 12.3 years). Comorbidity data were obtained with the Structured Clinical Interview for DSM-IV. BDD severity was assessed with the Yale-Brown Obsessive Compulsive Scale Modified for BDD, and delusionality (insight) was assessed with the Brown Assessment of Beliefs Scale. Quality of life and social/occupational functioning were examined using the Social Adjustment Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Medical Outcomes Study 36-Item Short-Form Health Survey, and Range of Impaired Functioning Tool. All variables were compared in BDD subjects with and without lifetime and current SUDs. Data were collected from January 2001 to June 2003. RESULTS: 48.9% of BDD subjects (N = 86) had a lifetime SUD, 29.5% had lifetime substance abuse, and 35.8% had lifetime substance dependence (most commonly, alcohol dependence [29.0%]). 17% (N = 30) had current substance abuse or dependence (9.1% reported current substance abuse, and 9.7% reported current dependence). 68% of subjects with a lifetime SUD reported that BDD contributed to their SUD. There were far more similarities than differences between subjects with a comorbid SUD and those without an SUD, although those with a lifetime SUD had a significantly higher rate of suicide attempts (p = .004). CONCLUSION: These preliminary results suggest that SUDs are very common in individuals with BDD. Subjects with and without a comorbid SUD were similar in most domains that were examined.

Adaptation, Psychological↗
PubMed2001

Comparison of corn silage hybrids for yield, nutrient composition, in vitro digestibility, and milk yield by dairy cows.

A study was undertaken to compare Novartis N29-F1, a dual-purpose 90-d relative maturity corn hybrid, and Novartis NX3018, a 90-d relative maturity leafy corn silage hybrid for dry matter (DM) yield, in vitro digestibility, plant components, nutrient composition, and lactational performance by Holstein cows. The two corn hybrids were planted in replicated 15.2- x 321-m plots. Plant population and DM yield were similar between the two corn hybrids. Novartis NX3018 had higher content of crude protein and ash, a higher proportion of leaves and stalks, and a lower proportion of grain compared with Novartis N29-F1. The cob, grain, and leaves of Novartis NX3018 had higher in vitro true DM and neutral detergent fiber disappearances compared with the respective plant components of Novartis N29-F1. Thirty-eight midlactation multiparous Holstein cows (78 +/- 23.0 days in milk) producing 47.2 +/- 8.9 kg of milk per cow per day were blocked and assigned randomly to one of two total mixed ration (TMR) containing (DM basis) approximately 26% Novartis N29-F1 or Novartis NX3018 corn silage. Cows were housed in a free-stall barn and group fed ad libitum. The lactation study was conducted as a crossover design with two 28-d periods. Samples and data were collected during the final 7 d of each period. The total mixed rations were formulated using the Cornell-Penn-Miner Dairy nutrition model. Cows that were fed the total mixed rations containing Novartis NX3018 corn silage produced higher yields of milk 3.5% fat-corrected milk (FCM), milk crude protein, and milk lactose compared to cows that were fed the TMR containing Novartis N29-F1 corn silage. In conclusion, the Novartis NX3018 corn hybrid was leafier and more digestible in vitro, and when fed to dairy cows as silage, promoted higher milk yield compared with the Novartis N29-F1 corn hybrid.

Animals↗
PubMed2003

First comparison of productivity and citrate donor load between the Trima version 4 (dual-stage filler) and the Trima Accel (single-stage filler) in the same donors.

BACKGROUND AND OBJECTIVES: Aside from new software the blood cell separator TRIMA (GambroBCT) also received a newly designed separation chamber offering a novel single stage separation technology, called Trima Accel. We evaluated this new system focusing on productivity and donor comfort by comparing it to the previous version (Trima version 4) in collecting single-donor platelet concentrates (SD-PCs) and plasma. MATERIALS AND METHODS: Each of 20 donors underwent platelet apheresis using both devices. We compared the collection efficiency (CE), the collections rate (CR), the volume of the collected plasma and the residual leukocytes. Furthermore we compared donor comfort in terms of duration of the donation, flow of citrate back to the donor and platelet and white blood cell (WBC) loss. RESULTS: While the number of collected platelets and the platelet concentration did not differ significantly between both techniques the time of the procedure was reduced by 15.6% with Trima Accel. This results in an increase of the CR and CE of 25% and 15% respectively when using Trima Accel. Log normal probability plotting of WBC counts showed that both techniques complied with the European and the US leukoreduction guidelines. The mean flow of ACDA to the donor per minute and per litre blood volume was also reduced by 20%. CONCLUSION: These data show that the Trima Accel represents a further improvement in apheresis platelet production with a better productivity and donor comfort, especially regarding the mean flow of ACDA to the donor.

Adult↗
PubMed2003

Mussel MAP, a major gonad-duct esterase-like protein, is released into sea water as a dual constituent of the seminal fluid and the spermatozoon.

Our interest in the comparative analysis of male reproductive-tract esterases in different animal groups has led us to undertake a detailed study of the Mytilus galloprovincialis male-associated polypeptide (MAP) throughout the mussel gonad-duct tract and at spawning. The results of this work indicate that MAP is a major protein in M. galloprovincialis semen, with dual presence in both sperm cells and cell-free seminal fluid. Shortly after spawning, the released sperm mass is subdivided in diffused cloudy-like and thread-shaped 'clots', in which a soluble-phase MAP may persist as long as the clots keep their compact form. Additional experiments involving the incubation of spawned spermatozoa at increasing Triton X-100 concentrations demonstrated that MAP is also strongly associated with sperm cells. These results were further validated by immunofluorescent staining, which revealed that MAP is localized in the mid-piece region of spawned spermatozoa. This unexpected finding raises the possibility that MAP may play a role in sperm fertility in bivalves. Using whole-mount histology and micromanipulation techniques, we studied the structural patterning of the mantle gonad-duct network and assessed the sampling of luminal contents from the ducts. Of particular interest is the observation that MAP content in the luminal fluid increases from the lumen of the spermatogenic tubules to that of the collecting gonad ducts, where MAP is detected at a very high concentration. These high levels may lead to a significant presence of MAP in semen and consequently to a prolonged survival of sperm spawned at sea. In addition, data related to the potential structural similarity between mussel MAP and esterase S of the Drosophila virilis ejaculatory bulb are presented and discussed. Finally, we show that the 64kDa protein of human semen reveals positive cross-reactivity with antibodies directed against Mytilus MAP and Drosophila esterase S. Taken together, the results reveal mussel MAP as the only esterase-like protein described so far whose distribution in the gonad and semen can be specifically associated with maturation, transport, emission and survival of spermatozoa outside.

Amino Acid Sequence↗
PubMed1992

Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population.

OBJECTIVE: Severe selenium deficiency has been documented in northern Zaïre, already known as one of the most iodine deficient regions in the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted in this area to evaluate the effects of a selenium supplementation on thyroid diseases. DESIGN: Placebo or selenium 50 micrograms as selenomethionine was administered once daily for 2 months. Blood and urine samples were collected before and after supplementation. PATIENTS: Fifty-two healthy schoolchildren from northern Zaire. MEASUREMENT: Selenium status, thyroid function and urinary iodide were determined. RESULTS: After 2 months of selenium supplementation, mean +/- SD serum T4 decreased from 73.1 +/- 45.4 to 48.3 +/- 23.7 nmol/l (P less than 0.001), serum FT4 from 11.8 +/- 6.7 to 8.4 +/- 4.1 pmol/l (P less than 0.01), and serum rT3 from 124 +/- 115 to 90 +/- 72 pmol/l (P less than 0.05), without significant change in serum T3 and serum TSH. CONCLUSION: Deiodinase type I which has been shown to be a seleno-enzyme could account for the changes in thyroid hormones in our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism in humans. Selenium could be an important cofactor in the clinical picture of iodine deficiency in Central Africa and could be involved in the aetiology of both forms of cretinism.

Administration, Oral↗
PubMed1994

The evolution of the dorsal thalamus of jawed vertebrates, including mammals: cladistic analysis and a new hypothesis.

The evolution of the dorsal thalamus in various vertebrate lineages of jawed vertebrates has been an enigma, partly due to two prevalent misconceptions: the belief that the multitude of nuclei in the dorsal thalamus of mammals could be meaningfully compared neither with the relatively few nuclei in the dorsal thalamus of anamniotes nor with the intermediate number of dorsal thalamic nuclei of other amniotes and a definition of the dorsal thalamus that too narrowly focused on the features of the dorsal thalamus of mammals. The cladistic analysis carried out here allows us to recognize which features are plesiomorphic and which apomorphic for the dorsal thalamus of jawed vertebrates and to then reconstruct the major changes that have occurred in the dorsal thalamus over evolution. Embryological data examined in the context of Von Baerian theory (embryos of later-descendant species resemble the embryos of earlier-descendant species to the point of their divergence) supports a new 'Dual Elaboration Hypothesis' of dorsal thalamic evolution generated from this cladistic analysis. From the morphotype for an early stage in the embryological development of the dorsal thalamus of jawed vertebrates, the divergent, sequential stages of the development of the dorsal thalamus are derived for each major radiation and compared. The new hypothesis holds that the dorsal thalamus comprises two basic divisions--the collothalamus and the lemnothalamus--that receive their predominant input from the midbrain roof and (plesiomorphically) from lemniscal pathways, including the optic tract, respectively. Where present, the collothalamic, midbrain-sensory relay nuclei are homologous to each other in all vertebrate radiations as discrete nuclei. Within the lemnothalamus, the dorsal lateral geniculate nucleus of mammals and the dorsal lateral optic nucleus of non-synapsid amniotes (diapsid reptiles, birds and turtles) are homologous as discrete nuclei; most or all of the ventral nuclear group of mammals is homologous as a field to the lemniscal somatosensory relay and motor feedback nuclei of non-synapsid amniotes; the anterior, intralaminar and medial nuclear groups of mammals are collectively homologous as a field to both the dorsomedial and dorsolateral (including perirotundal) nuclei of non-synapsid amniotes; the anterior, intralaminar, medial and ventral nuclear groups and the dorsal lateral geniculate nucleus of mammals are collectively homologous as a field to the nucleus anterior of anamniotes, as are their homologues in non-synapsid amniotes. In the captorhinomorph ancestors of extant land vertebrates, both divisions of the dorsal thalamus were elaborated to some extent due to an increase in proliferation and lateral migration of neurons during development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Menopause-related changes in body fat distribution.

Menopause-related changes in body fat distribution may partially explain the greater risk of cardiovascular and metabolic disease during the postmenopausal years. To date, however, the effect of the menopause transition on body fat distribution remains unclear. Cross-sectional and longitudinal studies using waist circumference or the waist-to-hip ratio show no effect of menopause on body fat distribution. By contrast, studies using dual-energy X-ray absorptiometry showed increased trunk fat in postmenopausal women. Moreover, studies using computed tomography (CT) and magnetic resonance imaging (MRI) show that postmenopausal women have greater amounts of intra-abdominal fat compared to premenopausal women. Collectively, these studies suggest that the menopause transition is associated with an accumulation of central fat and, in particular, intra-abdominal fat. Whether menopause-related differences in trunk or intra-abdominal fat are independent of age and/or adiposity, however, is unclear. Thus, we recently examined the effect of menopausal status on body composition and abdominal fat distribution in 53 middle-aged, premenopausal women (47 +/- 3 years) and 28 early postmenopausal women (51 +/- 4 years). Postmenopausal women had 36% more trunk fat (p < 0.01), 49% greater intra-abdominal fat area (p < 0.01), and 22% greater subcutaneous abdominal fat area (p < 0.05) than premenopausal women. The menopause-related difference in intra-abdominal fat persisted (p < 0.05) after statistical adjustment for age and fat mass, whereas no differences were noted in trunk or abdominal subcutaneous fat. A similar pattern of differences in trunk, subcutaneous, and intra-abdominal fat was observed in subsamples of pre- and postmenopausal women matched for age or fat mass. Our data and that of others suggest that early postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total adiposity. Thus, CT and MRI should be used when examining menopause-related changes in body fat distribution.

Absorptiometry, Photon↗
PubMed1993

Endothelin activation of phospholipase D: dual modulation by protein kinase C and Ca2+.

Previous work from this laboratory has identified an endothelin (ET) type A (ETA) receptor on cultured rat renal medullary interstitial cells (RMIC), coupled to phosphatidylinositol-specific phospholipase C (PI-PLC), dihydropyridine-insensitive receptor-operated Ca2+ channels, and phospholipase A2. The current studies explored a role for ET stimulation of phosphatidylcholine-specific phospholipase D (PC-PLD) in intracellular signaling of this cell type. ET stimulated PLD activation, as measured by phosphatidic acid (PA) or phosphatidylethanol (PEt) accumulation, in a time- and concentration-dependent manner. Inhibition of diacylglycerol (DAG) kinase by ethylene glycol dioctanoate or 6-(2)4-[(4-fluorophenyl)-phenylmethylene]-1-piperadinyl]ethy l-7-methyl-5H - thiaxolo-[3,2-alpyrimidin]-5-one (R 59022) failed to blunt PA accumulation, indicating that PLD, and not DAG, was the source of PA. Inhibition of PA phosphohydrolase (PAP) by propranolol increased late accumulation of PA, suggesting that the prevailing metabolic flow was in the direction of PA to DAG. Phorbol 12-myristate 13-acetate (PMA) augmented ET-evoked PEt accumulation, whereas downregulation of protein kinase C (PKC) obviated agonist-induced PEt production. PMA augmentation of PLD activity proceeded independent of cytosolic free Ca2+ concentration. Ca2+ derived from either intracellular or extracellular sources enhanced ET-related PEt accumulation but was without effect in PKC-downregulated cells. Collectively, these observations indicate that ET stimulates PLD production in RMIC. PKC is the major regulator of this process, with Ca2+ playing a secondary, modulatory role. In addition, these data suggest that PC-PLD is coupled to the ETA receptor.

Animals↗
PubMed2006

Comorbid substance use and age at onset of schizophrenia.

BACKGROUND: Substance use may be a risk factor for the onset of schizophrenia. AIMS: To examine the association between substance use and age at onset in substance use and age at onset in a UK, inner-city sample of people with recent-onset schizophrenia. METHOD: The study sample consisted of 152 people recruited to the West London First-Episode Schizophrenia Study. Self-reported data on drug and alcohol use, as well as information on age at onset of psychosis, were collected. Mental state, cognition (IQ, memory and executive function) and social function were also assessed. RESULTS: In total, 60% of the participants were smokers, 27% reported a history of problems with alcohol use, 35% reported current substance use (not including alcohol), and 68% reported lifetime substance use (cannabis and psychostimulants were most commonly used). Cannabis use and gender had independent effects on age at onset of psychosis, after adjusting for alcohol misuse and use of other drugs. CONCLUSIONS: The strong association between self-reported cannabis use and earlier onset of psychosis provides further evidence that schizophrenia may be precipitated by cannabis use and/or that the early onset of symptoms is a risk factor for cannabis use.

Adolescent↗
PubMedDate not supplied

Relationship between metabolic bone disease and bone mineral density measured by dual-energy X-ray absorptiometry in the green iguana (Iguana iguana).

The aim of our work was to study the feasibility of using dual-energy X-ray absorptiometry to obtain reference bone density values in relation to body weight, gender, and metabolic bone disease in the green iguana. The study was performed on 28 animals. The weight, age, and gender of each iguana were recorded. Each lizard was carefully examined and radiographed to detect signs of metabolic bone disease. Blood samples were collected from each animal to evaluate Ca/P and total protein. All animals, both affected (group B; n = 11) and unaffected (group A; n = 17) by metabolic bone disease, were individually scanned using an X-ray densitometer. The regions of interest were the head, lumbar spine, right, and left femur. Statistical analysis was performed separately for each region of interest. Body weight had the strongest relationship with bone density (P < 0.01). Within regions of interest, for iguanas of average weight (710 g), statistically significant differences between healthy and sick animals were found: head (0.140 vs. 0.090 g/cm2; P < 0.01); lumbar spine (0.164 vs. 0.107 g/cm2; P < 0.01); right femur (0.103 vs. 0.076 g/cm2; P < 0.01); left femur (0.103 vs. 0.078 g/cm2; P < 0.01). Regression equations to obtain reference values of bone density as a function of body weight for animals affected and not affected by metabolic bone disease are provided. Our data indicate that X-ray bone densitometry is an additional tool for studying bone pathophysiology in reptiles.

Absorptiometry, Photon↗
PubMed1997

Prediction of compliance with outpatient referral in patients with schizophrenia and psychoactive substance use disorders.

BACKGROUND: Most patients with concurrent schizophrenia and psychoactive substance use disorders may be adequately treated as outpatients. However, many do not comply with outpatient referrals and are therefore at heightened risk for rehospitalization. METHOD: Drawing on standardized interview data collected during an index hospitalization, we developed a logistic regression model to predict compliance with outpatient treatment. The model was tested on a confirmatory sample, and its sensitivity and specificity were further evaluated in a cross-validation study of 1000 random samples. RESULTS: In a reference sample, the logistic function distinguished compliant from noncompliant patients in 37 (76%) of 49 cases. In a confirmatory sample, compliance status was predicted for 11 (78%) of 14 patients with a sensitivity of 1.00 and a specificity of 0.67. Women and patients with negative syndrome schizophrenia were compliant with outpatient referral, whereas those with mixed syndromes were most likely to be noncompliant. Cross-validation supports the stability of the model. CONCLUSION: While most persons with schizophrenia and concurrent substance abuse comply with integrated outpatient treatment, most who cannot may be predicted in advance.

Adult↗
PubMed2005

[Psychiatric morbidity and alcohol use by pregnant women in a public obstetric service].

OBJECTIVE: To investigate the relationship between alcohol consumption and emotional distress in pregnant women, and to verify whether women with problematic alcohol consumption (abuse or dependence) have more emotional distress than those with non-problematic alcohol consumption. METHODS: A cross-sectional observational study was carried out in a clinical sample from a public obstetric service in Ribeirão Preto, Brazil. A non-probabilistic convenience sample of patients who were consecutively recruited comprised 450 pregnant women. Three questionnaires were applied: a sociodemographic profile, followed by the Psychiatric Morbidity Questionnaire (QMPA) and a standardized questionnaire for collecting data on alcohol-related problems (abuse or dependence) according to ICD-10 criteria. Univariate analysis (ANOVA) was used for comparison between groups using central distribution measures and 95% confidence intervals. RESULTS: There were found 172 (38.2%) problematic pregnant women with positive score (score >7) in the QMPA. A group of 41 (9.1%) pregnant women with problematic alcohol consumption was detected according to ICD-10 criteria, 27 (6.0%) of them diagnosed as alcohol abuse and 14 (3.1%) as alcohol dependence. Alcohol abuse or dependence syndrome was related to greater emotional distress, i.e. higher mean scoring in anxiety, depression and alcohol QMPA subscales. CONCLUSIONS: Given the prevalence of emotional distress and alcohol consumption during pregnancy and high risk of mother-child health problems, careful evaluations in this population should be conducted by health professionals.

Alcohol Drinking↗
PubMed2004

The dual response of protein kinase Fyn to neural trauma: early induction in neurons and delayed induction in reactive astrocytes.

In the developing central nervous system, a src-related protein-tyrosine kinase fyn participates in the myelination process, neuronal growth, and cytoskeletal organization. In adults, fyn has been implicated in learning and memory formation. To test if fyn expression is modulated by neuronal activity, we performed quantitative in situ hybridization (ISH) using brain sections of the adult rats that had undergone either kainic acid (KA)-induced seizures or neuronal deafferentation (entorhinal cortex lesion, ECL). In the KA model, a few hours after seizure activities, fyn mRNA was elevated in the dentate gyrus (DG) (+45%), cerebral cortex layer III (+35%), and piriform cortex (+25%). Conversely, fyn mRNA consistently decreased in the hippocampal neurons after transection of the major axonal inputs from the entorhinal cortex. Although fyn expression in the brain has been allegedly limited to neurons and oligodendrocytes, we provide in this study the first evidence that fyn mRNA is highly expressed in the astrocytes involved in reactive gliosis. In the KA model, the occurrence of fyn-overexpressing astrocytes increased with the progress of neuronal damage in the CA1 and CA3 regions of the hippocampus. In contrast, fyn-overexpressing astrocytes were not observed in the granular cell layer of dentate gyrus (DG), where neurons were not damaged. Likewise, in the ECL model, the most drastic change in fyn mRNA expression took place at the reactive astrocytes near the stab wound sites, where fyn mRNA levels were doubled 4-10 d after the lesion. Collectively, our data suggest that (i) an early induction of fyn mRNA in neurons is linked to neuronal activity, and (ii) the delayed induction of fyn mRNA in reactive astrocytes near the damaged cells may play novel signaling roles during glial response.

Animals↗
PubMed2006

A dominant role for chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) in mediating chemotaxis of CRTH2+ CD4+ Th2 lymphocytes in response to mast cell supernatants.

Human cultured mast cells, immunologically activated with immunoglobuin E (IgE)/anti-IgE, released a factor(s) that promoted chemotaxis of human CRTH2+ CD4+ T helper type 2 (Th2) lymphocytes. Mast cell supernatants collected at 20 min, 1 hr, 2 hr and 4 hr after activation caused a concentration-dependent increase in the migration of Th2 cells. The effect of submaximal dilutions of mast-cell-conditioned media was inhibited in a dose-dependent manner by ramatroban (IC50 = 96 nm), a dual antagonist of both the thromboxane-like prostanoid (TP) receptor and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), but not by the selective TP antagonist SQ29548, implicating CRTH2 in mediating the chemotactic response of these Th2 cells. The effect of mast-cell-conditioned media was mimicked by prostaglandin D2 (PGD2) and this eicosanoid was detected in the conditioned media from activated mast cells in concentrations sufficient to account for the activity of the mast cell supernatants. Treatment of the mast cells with the cyclo-oxygenase inhibitor diclofenac (10 microm) inhibited both the production of PGD2 and the CRTH2+ CD4+ Th2-stimulatory activity, while addition of exogenous PGD2 to conditioned media from diclofenac-treated mast cells restored the ability of the supernatants to promote chemotaxis of these Th2 cells. The degree of inhibition caused by diclofenac treatment of the mast cells was concordant with the degree of inhibition of chemotactic responses afforded by CRTH2 blockade. These data suggest that PGD2, or closely related metabolites of arachidonic acid, produced from mast cells may play a central role in the activation of CRTH2+ CD4+ Th2 lymphocytes through a CRTH2-dependent mechanism.

Carbazoles↗
PubMed2001

Light-dependent induction of cFos during subjective day and night in PACAP-containing ganglion cells of the retinohypothalamic tract.

Environmental light stimulation via the retinohypothalamic tract (RHT) is necessary for stable entrainment of circadian rhythms generated in the suprachiasmatic nucleus (SCN). In the current report, the authors characterized the functional activity and phenotype of retinal ganglion cells that give rise to the RHT of the rat. Retinal ganglion cells that give rise to the RHT were identified by transsynaptic passage of an attenuated alpha herpesvirus known to have selective affinity for this pathway. Dual labeling immunocytochemistry demonstrated co-localization of viral antigen and pituitary adenylate cyclase activating polypeptide (PACAP) in retinal ganglion cells. This was confirmed using the anterograde tracer cholera toxin subunit B (ChB). In normal and retinally degenerated monosodium glutamate (MSG)-treated rats, ChB co-localized with PACAP in axons of the retinorecipient zone of the SCN. Light-induced Fos-immunoreactivity (Fos-IR) was apparent in all PACAP-containing retinal ganglion cells and a population of non-PACAP-containing retinal ganglion cells at dawn of normal and MSG-treated animals. Within the next 3 h, Fos disappeared in all non-PACAP-immunoreactive cells but persisted in all PACAP-containing retinal ganglion cells until dusk. When animals were exposed to constant light, Fos-IR was sustained only in the PACAP-immunoreactive (PACAP-IR) retinal ganglion cells. Darkness eliminated Fos-IR in all PACAP-IR retinal ganglion cells, demonstrating that the induction of Fos gene expression was light dependent. When animals were maintained in constant darkness and exposed to light pulses at ZT 14, ZT 19, or ZT 6, Fos-IR was induced in PACAP-IR retinal ganglion cells in a pattern similar to that seen at dawn. Collectively, these data indicate that PACAP is present in ganglion cells that give rise to the RHT and suggest a role for this peptide in the light entrainment of the clock.

Animals↗
PubMed1996

Microdosimetric evaluation of relative biological effectiveness for 103Pd, 125I, 241Am, and 192Ir brachytherapy sources.

PURPOSE: To determine the microdosimetric-derived relative biological effectiveness (RBE) of 103Pd, 125I, 241Am, and 192Ir brachytherapy sources at low doses and/or low dose rates. METHODS AND MATERIALS: The Theory of Dual Radiation Action can be used to predict expected RBE values based on the spatial distribution of energy deposition at microscopic levels from these sources. Single-event lineal energy spectra for these isotopes have been obtained both experimentally and theoretically. A grid-defined wall-less proportional counter was used to measure the lineal energy distributions. Unlike conventional Rossi proportional counters, the counter used in these measurements has a conducting nylon fiber as the central collecting anode and has no metal parts. Thus, the Z-dependence of the photoelectric effect is eliminated as a source of measurement error. Single-event spectra for these brachytherapy sources have been also calculated by: (a) the Monte Carlo code MCNP to generate the electron slowing down spectrum, (b) transport of monoenergetic electron tracks, event by event, with our Monte Carlo code DELTA, (c) using the concept of associated volume to obtain the lineal energy distribution f(y) for each monoenergetic electron, and (d) obtaining the composite lineal energy spectrum for a given brachytherapy source based on the electron spectrum calculated at step (a). RESULTS: Relative to 60Co, the RBE values obtained from this study are: 2.3 for 103Pd, 2.1 for 125I, 2.1 for 241Am, and 1.3 for 192Ir. CONCLUSIONS: These values are consistent with available data from in vitro cell survival experiments. We suggest that, at least for these brachytherapy sources, microdosimetry may be used as a credible alternative to time-consuming (and often uncertain) radiobiological experiments to obtain information on radiation quality and make reliable predictions of RBE in low dose rate brachytherapy.

Americium↗