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Biomedical subjects

S A Joseph

Publications and source records attributed to S A Joseph.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced cyclooxygenase-2 expression in olfactory-limbic forebrain following kainate-induced seizures.

Cyclooxygenase-2 is expressed at low levels in a subset of neurons in CNS and is rapidly induced by a multiplicity of factors including seizure activity. A putative relationship exists between cyclooxygenase-2 induction and glutamatergic neurotransmission. Cyclooxygenase-1 is constitutively expressed in glial cells and has been specifically linked to microglia. In this study we evaluated cyclooxygenase-2 protein immunocytochemically and found markedly enhanced immunostaining primarily in olfactory-limbic regions at 2, 6 and 24 h following kainate-induced status epilepticus. Impressive enhanced cyclooxygenase-2 immunoreactivity was localized in anterior olfactory nucleus, tenia tecta, nucleus of the lateral olfactory tract, piriform cortex, lateral and basolateral amygdala, orbital frontal cortex, nucleus accumbens (shell) and associated areas of ventral striatum, entorhinal cortex, dentate gyrus granule cells and hilar neurons, hippocampal CA subfields and subiculum. Alternate sections were processed for dual immunocytochemical analysis utilizing c-Fos and cyclooxygenase-2 antiserum to examine the possibility that the neuronal induction of cyclooxygenase-2 was associated with seizure activity. Neurons that showed a timeline of cyclooxygenase-2 upregulation were found to possess c-Fos immunopositive nuclei. Additional results from all seizure groups showed cyclooxygenase-1 induction in microglia, which was confirmed by Western blot analysis of hippocampus. Western blot and real-time quantitative RT-PCR analysis showed significant upregulation of cyclooxygenase-2 expression, confirming its induction in neurons. These data indicate that cyclooxygenase-2 induction in a neuronal network can be a useful marker for pathways associated with seizure activity.

Animals↗
PubMed2006

P2X7 receptor immunoreactive profile confined to resting and activated microglia in the epileptic brain.

The purpose of this study was to identify the CNS cellular constituent immunoreactive for specific P2X7 receptor antiserum in the kainate-induced seizure and non-seizure rat brain. Analysis of P2X7 immunocytochemistry (ICC) revealed small immunoreactive cells with processes showing distinct morphological changes as seizures progressed in time. These morphological changes were reminiscent of reactive glia during CNS injury. In order to determine the identity of this non-neuronal cellular constituent, we employed dual ICC techniques using sequential antibody incubations and reacted the sections with contrasting chromagens. Specific glial markers tested in the series included Iba1 (microglia), COX-1 (microglia), and GFAP (astroglia). Results of this study revealed distinct colocalization when sections immunostained for P2X7 were dual immunostained with antisera specific for microglia (Iba1, COX-1). In contrast, no colocalization was evident when sections were dual immunostained with P2X7 and GFAP, an astrocytic marker. In the latter experiment, dual ICC revealed two distinct cell populations with contrasting color demonstrating a population of distinct GFAP immunopositive cells and a population of distinct P2X7 immunopositive cells. We conclude that P2X7 antiserum used in this study is specific for and identifies microglia in rat and that there exists a timeline of progressive changes in microglia morphology that can be demonstrated following kainate-induced seizures. In addition, the morphological changes in microglia following seizure induction that can be identified with P2X7 antisera or with antisera specific for microglia suggest a neuroinflammatory milieu in areas of CNS seizure activity.

Animals↗
PubMed2004

AMPA receptor alterations precede mossy fiber sprouting in young children with temporal lobe epilepsy.

Following neurological injury early in life numerous events, including excitotoxicity, neural degeneration, gliosis, neosynaptogenesis, and circuitry reorganization, may alone or in concert contribute to hyperexcitability and recurrent seizures in temporal lobe epilepsy. Our studies provide new evidence regarding the temporal sequence of key elements of hippocampal reorganization, mossy fiber sprouting and glutamate receptor subunit up-regulation, in a subset of young temporal lobe epileptic patients. Without evidence of mossy fiber sprouting, the youngest age group (3-10 years old) of mesial temporal lobe epileptic patients demonstrated enhanced glutamate receptor subunit profiles, suggesting that the dendritic change precedes axonal sprouting. However, sclerotic hippocampal specimens from epileptic patients ages 12-15 years old had the characteristic features of glutamate receptor up-regulation and mossy fiber sprouting first identified in the adult, indicating that reconstructed circuits appear early in the course of the disease. Non-sclerotic hippocampal specimens from lesion associated temporal lobe epileptic patients of all age groups showed minimal cell loss, sparse staining of glutamate receptor subunits in the dentate gyrus, and little or no mossy fiber sprouting. These compelling findings suggest a progressive sequence of events in the reorganization of the dentate gyrus of sclerotic hippocampal specimens. We suggest that cell loss and up-regulation of glutamate receptor subunits appear early in temporal lobe epilepsy and contribute to the synaptic plasticity that may facilitate the subsequent sprouting of mossy fiber collaterals which compound an already precipitous state of decline. The combination of pre-synaptic and post-synaptic changes serves as a potential substrate for hyperexcitability.

Adolescent↗
PubMed2000

Effect of nitric oxide donors on the central nervous system--nitroglycerin studies in the rat.

The demonstration that nitrovasodilators act as nitric oxide (NO) donors has favored a resurgence of interest in this class of compounds. The demonstration of the different biological effects of NO in various districts, including the central nervous system, suggests a possible role for these substances besides their well-known cardiovascular activity. Among the various nitrovasodilators commercially available, nitroglycerin represents a well known substance to headache experts because of its capability to provoke spontaneous-like migraine attacks in headache-free migrainous subjects. Basic research has recently demonstrated that nitroglycerin activates a variegate set of brain nuclei following systemic administration via the intervention of selected neurotransmitters and neuromediators, with a specific time-pattern in different brain areas. Increasing evidence suggests that nitroglycerin-induced neuronal activation is mediated by multiple mechanisms that include direct neuronal and vascular action of nitroglycerin-derived and endogenously-synthesized NO, as well as indirect effects related to nitroglycerin-induced changes in cardiovascular and trigeminovascular systems. The study of the neurovascular effects of nitroglycerin in the rat provides relevant information for a better understanding of the pathophysiology of migraine attacks and of their triggers.

Animals↗
PubMed1999

Reciprocal circuits involved in nitroglycerin-induced neuronal activation of autonomic regions and pain pathways: a double immunolabeling and tract-tracing study.

This study uses tract-tracing protocols to determine the circuitry of specific nuclei involved in nitroglycerin-induced activation. Combined retrograde and anterograde tracers were injected into nuclei which consistently demonstrate robust Fos expression following our systemic nitroglycerin injection paradigm. The nuclei, which conform to these criteria, that we have evaluated in this study are the locus coeruleus, parabrachial nucleus and paraventricular nucleus of the hypothalamus. Dual Fos/tracer immunocytochemistry in treated animals documented the existence of a subset of autonomic nuclei which are activated by nitroglycerin injection and have reciprocal connections. From the nature of this rich interconnection we suggest that nitroglycerin activates autonomic responses involved in cardiovascular pressor mechanisms. Nuclei which show strong Fos labeling following nitroglycerin administration, but not traced in this study, include the nucleus trigeminalis caudalis and the ventrolateral column of the periaqueductal gray, both of which mediate nociceptive modalities. These data confirm and expand on our previous findings and demonstrate that nitroglycerin activates a complex set of structures that are functionally and structurally interconnected to articulate an integrated response.

Animals↗
PubMed1999

The effects on the central nervous system of nitroglycerin--putative mechanisms and mediators.

Nitroglycerin is an organic nitrate that has been used as a vasodilator in the treatment of cardiac diseases for over a century. Only recently it has been demonstrated that the vasodilator effect of this drug depends upon the formation of nitric oxide in the blood vessel wall. However, clinical and research data gathered during the last decades have suggested that nitroglycerin possesses, besides its peripheral vasodilator effect, additional, puzzling biological activities. This organic nitrate compound provokes reflex cardiovascular activities via its interaction with the central sympathetic system. Its cerebrovascular effect, on the other hand, is probably mediated by the local release of neuropeptides. The direct application of nitroglycerin onto brain nuclei causes a prompt increase in the neuronal discharge rate. From a neurological point of view, nitroglycerin consistently induces a specific headache attack in patients suffering from migraine. Because of its temporal pattern and clinical characteristics, nitroglycerin-induced headache cannot be solely ascribed to the a drug-induced vasorelaxation. The demonstration that systemic nitroglycerin administration activates a widespread set of vegetative, nociceptive and neuroendocrine structures in the central nervous system seems to further support the occurrence of central mechanisms in the biological activity of nitroglycerin. Double labeling immunocytochemical and neuropharmacological studies have provided information on the putative neurotransmitters and neurochemical mechanisms involved in nitroglycerin-induced neuronal activation.

Animals↗
PubMed1999

Measurement of delusional ideation in the normal population: introducing the PDI (Peters et al. Delusions Inventory).

The Peters et al. Delusions Inventory (PDI) was designed to measure delusional ideation in the normal population, using the Present State Examination as a template. The multidimensionality of delusions was incorporated by assessing measures of distress, preoccupation, and conviction. Individual items were endorsed by one in four adults on average. No sex differences were found, and an inverse relationship with age was obtained. Good internal consistency was found, and its concurrent validity was confirmed by the percentages of common variance with three scales measuring schizotypy, magical ideation, and delusions. PDI scores up to 1 year later remained consistent, establishing its test-retest reliability. Psychotic inpatients had significantly higher scores, establishing its criterion validity. The ranges of scores between the normal and deluded groups overlapped considerably, consistent with the continuity view of psychosis. The two samples were differentiated by their ratings on the distress, preoccupation, and conviction scales, confirming the necessity for a multidimensional analysis of delusional thinking. Possible avenues of research using this scale and its clinical utility are highlighted.

Adult↗
PubMed1998

Localization of corticotropin-releasing factor in primary and secondary lymphoid organs of the rat.

Cells of the immune system produce a variety of neuropeptides or peptide hormones, either constitutively or upon induction, and possess specific neuropeptide receptors that display ligand-receptor interactions similar to those described in the central nervous system (CNS). These findings suggest that specific subsets of lymphoid cells can produce and respond to peptides previously thought to be principally neural mediators. Recently, corticotropin releasing factor (CRF) mRNA was detected in the rat thymus and spleen, although the cells that synthesize CRF were not identified. We examined the localization of CRF and its mRNA in the rat spleen, thymus, and mesenteric lymph nodes using immunocytochemistry (ICC) and in situ hybridization (ISH), respectively. Immunoreactive CRF was present in cells in the marginal zone and red pulp of the spleen, in connective tissue septa and the subcapsular region of the thymus, and in the medullary cords and sinuses of the mesenteric lymph nodes. Dual ICC/ISH for CRF and its mRNA, respectively, demonstrated CRF mRNA over CRF-immunoreactive cells, suggesting CRF synthesis. Double-label ICC for CRF and markers for specific immunocyte subsets suggest that CRF+ cells in the spleen and thymus are macrophages. CRF+ cells in primary and secondary lymphoid organs reside in compartments that are innervated by sympathetic nerves, and some cells appears to be contacted by noradrenergic sympathetic nerve fibers, suggesting that CRF release may be influenced by the sympathetic nervous system, as it is in the hypothalamo-pituitary-adrenal axis. The presence of CRF in organs of the immune system suggests that this neuropeptide may modulate immune functions after paracrine release.

Animals↗
PubMed1997

Neurochemical mechanisms of nitroglycerin-induced neuronal activation in rat brain: a pharmacological investigation.

Nitroglycerin is a nitric oxide donor which induces sustained expression of Fos protein, a marker of neuronal activation, in specific neuronal groups in the central nervous system. The mechanisms which underlie nitroglycerin-induced neuronal activation are elusive at this time, although a precise role has been suggested for the pool of neurons containing nitric oxide synthase as well as for catecholaminergic and peptidergic pathways. The aim of this study was to provide further details on the central effect of nitroglycerin by means of a pharmacological manipulation of nitroglycerin-induced neuronal activation with inhibitors of the nitric oxide synthase, modulators of the sympathetic drive and mediators of pain perception. Adult male Sprague-Dawley rats received L-NGnitro-arginine methyl ester, 7-nitro-indazole, ephedrine sulfate, indomethacin, capsaicin or vehicle before the subcutaneous injection of nitroglycerin (10 mg/kg b.w.). They were sacrificed 4 hr after nitroglycerin administration and brain sections were processed for immunocytochemical visualization of Fos. All the pharmacological treatments administered before injecting nitroglycerin selectively influenced Fos expression in the different brain nuclei. The data obtained suggest that nitroglycerin-induced neuronal activation is mediated by nociceptive and barosensitive mechanisms. Nitric oxide seems to represent the most important mediator of this phenomenon. The sympathetic system and prostaglandin synthesis are also likely to be involved.

Animals↗
PubMed1997

Systemic lupus erythematosus complicating complement type 2 deficiency: successful treatment with fresh frozen plasma.

We report a man who presented in 1981 at the age of 30 with cutaneous lupus erythematosus (LE), which was resistant to a range of treatments over the subsequent 11 years. In 1991 he suffered fits, dysphasia and agitated depression, and in 1992 a severe septicaemic illness. Systemic LE was diagnosed, and investigation showed homozygous complement type 2 deficiency (C2d). Over a period of 30 months he has received 6 weekly fresh frozen plasma. Since starting this treatment his cutaneous disease has resolved and his depression, verbal fluency and psychomotor scores improved. We have not observed any adverse effects to this treatment and suggest it should be considered in similar patients.

Adult↗
PubMed1996

Systemic nitroglycerin activates peptidergic and catecholaminergic pathways in rat brain.

In this study, we carried out an immunohistochemical evaluation of the neurochemical characteristics of neurons that are activated (i.e., express Fos protein) in response to systemic administration of nitroglycerin. In the brain stem, a significant percentage of activated neurons contained noradrenaline as a neurotransmitter, whereas only a few of them contained serotonin. In the paraventricular and supraoptic nuclei of the hypothalamus, numerous Fos-immunoreactive neurons were also positive for vasopressin, oxytocin, and corticotropin-releasing factor. Codistribution with corticotropin-releasing factor was also observed in the central nucleus of the amygdala. Our findings point out a prominent role for catecholaminergic and peptidergic pathways in the brain in response to systemic nitroglycerin.

Animals↗
PubMed1996

NF-kappa B transcription factor subunits in rat brain: colocalization of p65 and alpha-MSH.

The subunit proteins p50 and p65 of the transcription factor NF-kappa B inhibitory protein were immunocytochemically identified and mapped in rat brain. The p65 subunit was localized to the cytoplasm of neurons in the lateral hypothalamus and colocalized with alpha-MSH in neurons identified as the alpha-2 component of the alpha-MSH system. The p50 subunit protein was distributed throughout the neocortex, basal ganglia, thalamic, and hypothalamic nuclei, and certain nuclei of the pons and medulla. The I-kappa B protein, which is necessary for the cytoplasmic sequestration of the NF-kappa B transcription factor complex, was identified specifically in regions of limbic, hypothalamic, and autonomic nuclei.

Animals↗
PubMed1996

Distribution of AMPA receptor subunits in the hippocampal formation of temporal lobe epilepsy patients.

The immunocytochemical distribution of the AMPA-selective receptor subunits GluR1 and GluR2/3 were mapped in the human hippocampal formation obtained from surgery for medically intractable temporal lobe epilepsy. GluR2/3 immunoreactivity was detected in all principal cell types of the hippocampal formation, including hilar neurons, granule cells of the dentate gyrus, and pyramidal cells of the cornu ammonis fields and subiculum. GluR2/3 immunostaining typically filled the cell bodies and processes of neurons. A comparison of GluR2/3 immunoreactivity in a sclerotic specimen versus a non-sclerotic specimen demonstrated a profound loss of staining, specifically in the areas where neuronal dropout was occurring, including CA1, CA3 and the hilus. An analysis of GluR1 immunoreactivity in non-sclerotic specimens revealed that it was predominantly localized to cellular processes throughout the cornu ammonis fields, with a sparse staining of the dentate gyrus outer molecular layer and little to no staining of the dentate gyrus inner molecular layer. Similar to the GluR2/3-immunostained patterns, GluR1 immunoreactivity was lost in the cornu ammonis fields of sclerotic hippocampal specimens, corresponding to patterns of neuronal dropout. Our most compelling finding was a unique extensive pattern of GluR1 and Glu2/3 immunoreactivity throughout the molecular layers of the dentate gyrus of severely compromised hippocampi. The altered staining of GluR1 and GluR2/3 complements some of the patterns of axonal sprouting already described for the dentate gyrus, with a conjecture that their anatomy and distribution pattern underlies to some degree the reorganization of the sclerotic hippocampus. A combination of enhanced glutamatergic transmission and changes in neuropeptides that modulate hippocampal circuitry could greatly affect the degree of excitability in the hippocampal formation. The alterations of GluR1 and GluR2/3 immunoreactivity in the dentate gyrus add another component to the concept of reorganization in the epileptic sclerotic hippocampus.

Adolescent↗
PubMed1996

Adrenocorticotropic hormone immunoreactivity in the hippocampal formation of temporal lobe epilepsy patients.

PURPOSE: We wished to identify immunocytochemically the distribution of proopiomelanocortin-related peptides in the hippocampal formation of patients with epilepsy. METHODS: Surgical hippocampal specimens from temporal lobe epilepsy (TLE) patients and autopsy control tissue were examined immunocytochemically for ACTH, alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin. RESULTS: There was a dense distribution of ACTH-immunoreactive neurons in the hippocampal formation of patients with mesial TLE syndrome (MTLE). These hippocampal specimens showed significant cell loss. ACTH-positive neurons were most prominent in the subiculum, with scattered ACTH-immunoreactive neuronal elements distributed in the cornu ammonis fields and hilus. Light ACTH immunoreactivity was detected in the tumor-related epileptic hippocampal specimens, which showed minimal cell loss. Although autopsy control tissue from the hypothalamus showed intense ACTH staining patterns in cells and fibers, there was little or no ACTH immunoreactivity in the autopsy hippocampal tissue. The expression of ACTH immunoreactive elements was correlated with patterns of cell loss. No alpha-MSH- or beta-endorphin-immunoreactive neurons were detected in any of the hippocampal specimens. CONCLUSIONS: ACTH has anticonvulsant properties, and its novel expression in the glutamatergic subicular neurons, which provide the main outflow of the hippocampal formation, may represent an attempt by the damaged hippocampal circuit to restore the balance of excitatory/inhibitory neurotransmission in TLE.

Adrenocorticotropic Hormone↗
PubMed1995

Measurement of serum bile acids concentrations for diagnosis of hepatobiliary disease in cats.

Serum bile acid concentrations were measured after food had been withheld for 12 hours (fasting serum bile acid [FSBA] concentration) and 2 hours after a meal (post-prandial serum bile acid [PSBA] concentration) using a direct enzymatic procedure in 108 cats clinically suspected of having hepatobiliary disease. In all cats, liver tissue was examined histologically to confirm the diagnosis. Twenty-six cats did not have histologic evidence of hepatobiliary disease and served as controls. The remaining 82 cats had hepatobiliary disease including hepatic lipidosis (n = 20), portosystemic vascular anomaly (n = 24), hepatic necrosis (n =13), hepatic neoplasia (n = 8), or cholestatic hepatic disease(n = 17). Sensitivity and specificity of measuring FSBA and PSBA concentrations were calculated for each test alone and when results were interpreted in combination (ie, in series and in parallel), and were compared with sensitivity and specificity of routinely used serum biochemical tests, including measuring serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase, and measuring serum concentrations of cholesterol, BUN, and total bilirubin. When tests were considered individually, determination of FSBA and PSBA concentrations had higher specificity than did the other tests (using a cutoff of 15 mumol/L for FSBA concentration and of 20 mumol/L for PSBA concentration). Determination of PSBA concentration had the highest sensitivity of all single tests in cats with hepatic lipidosis, portosystemic vascular anomaly, or cholestasis; determination of alanine aminotransferase activity or PSBA concentration had the highest sensitivity for cats with hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

NADPH-diaphorase activity and Fos expression in brain nuclei following nitroglycerin administration.

Organic nitrates are considered nitric oxide donors in that they have been shown to form nitric oxide in vitro and in vivo. Nitroglycerin is an organic nitrate which possesses peculiar activities mediated, to some extent, by the central nervous system via the noradrenergic system. Previous reports have shown that systemic nitroglycerin is able to induce Fos expression in brain nuclei which are known to contain nitric oxide synthesizing enzyme. Neuronal NADPH-diaphorase has been shown to be a nitric oxide synthase. Thus, in this study we used NADPH-diaphorase histochemistry to evaluate the distribution of Fos-immunoreactive cells within neurons which contain nitric oxide synthase. The data showed co-localization of Fos with NADPH-diaphorase activity in numerous neurons of the paraventricular and supraoptic nuclei of the hypothalamus. In the brainstem, a few neurons were doubly labeled for Fos and NADPH-diaphorase activity, but NADPH-diaphorase positive fibers and Fos-immunoreactive neurons were consistently co-distributed in the locus coeruleus, parabrachial nucleus, nucleus tractus solitarius and spinal trigeminal nucleus caudalis. These findings demonstrate that nitroglycerin administration activates a selective group of neurons which are a source of nitric oxide or which are in close proximity with neuronal processes containing nitric oxide synthase, and suggest that the nitric oxide synthase synthesizing pathway may be involved at various levels in the central effect of nitroglycerin.

Animals↗