Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate adenocarcinoma (PA) is known to metastasize widely to bone, lung, lymph nodes, and other sites. We have observed a rare, although distinctive, neuroendocrine (NE) cytomorphology of metastatic PA on fine-needle aspiration (FNA) that mimics small cell carcinoma (SCC). From a total of 117 cases, eight cases of metastatic PA diagnosed on FNA showed cytomorphologic features indistinguishable from SCC. All specimens were reviewed, along with immunoperoxidase (IPOX) studies using prostate specific (PSA, PSAP) and NE markers (synaptophysin, chromogranin, etc.). The patients ranged in age from 51-68 (mean age = 63). The PSA levels at the time of FNA ranged from <0.1 to 2,892 ng/ml (normal postprostatectomy <0.2 ng/ml). Sites of FNA included liver (two), soft tissue (five), and lymph node (one). FNA was performed from 11 mo to 6 yr after the initial diagnosis of the primary tumor. All primary PA were of high Gleason grade ranging from 7-9. None of the primary PA showed neuroendocrine morphology. Cytomorphologic characteristics observed on FNA included predominantly single cells with occasional sheets or loose cell aggregates. A predominant NE nuclear morphology was evident (i.e., hyperchromasia, fine dusty chromatin, inconspicuous nucleoli, nuclear molding, chromatinic crush artifact, karyorrhexis, mitoses, etc.), with none of the tumors displaying glandular formation. Taken together, these features gave these metastases a cytomorphology indistinguishable from SCC. IPOX studies revealed PSA-positivity (5/7), PSAP-positivity (4/7), and only focal NE markers positivity (3/6). Metastatic prostate carcinoma may rarely mimic a SCC (6.8% in this study). This often necessitates further patient workup to identify the primary source for the patient's metastasis, particularly if the patient has multiple lesions. An accurate diagnosis of these lesions as PA metastases is essential for effective, timely treatment and therapeutic design.
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PMID:Prostatic adenocarcinoma metastases mimicking small cell carcinoma on fine-needle aspiration. 1220 72

Morphological changes in the gonadotropin releasing hormone (GnRH) neurons in the preoptic area (POA) and their terminals in the median eminence-arcuate (ME-ARC) region are reported to occur during ovarian cycle that may be involved in the GnRH release into the portal blood during preovulatory surge. However, the neuronal substrates participating in altered GnRH neuronal plasticity are poorly understood. The present study was designed to determine whether morphological changes occurring in the GnRH neuron cell bodies in the POA and their terminals in the ME-ARC region of hypothalamus with pulsatile GnRH release in cycling female rats are associated with expression of intrinsic determinants of neuronal plasticity. The plasticity markers studied are polysialylated neural cell adhesion molecule (PSA-NCAM), high molecular weight isoforms of NCAM, growth associated protein (GAP-43), glial fibrillary acidic protein (GFAP) and synaptophysin. Regularly cycling female rats were sacrificed at diestrous, i.e., when GnRH release is low, and at proestrous, i.e., when preovulatory GnRH surge occurs, using perfusion fixation method for immunohistochemical staining of GnRH cells. GnRH cell bodies and their terminals from the POA and ME-ARC region respectively, were localized using immunohistochemical technique in proestrous and diestrous phase of estrous cycle and our results showed a marked increase in the GnRH nerve terminals length and immunoreactivity in the ME-ARC region from proestrous phase rats as compared to diestrous rats. Immunoblot analyses of the POA and ME-ARC region of the hypothalamus revealed a significant increase in the content of PSA-NCAM, NCAM-180, NCAM-140, GAP-43 and synaptophysin from proestrous phase rats as compared to diestrous phase rats. The ME-ARC region showed more pronounced increase in the protein expression of these markers of neuronal plasticity as compared to the POA, whereas, hippocampal region did not show any significant change in the content of these markers showing specificity of the changes to the GnRH system. GFAP content was significantly decreased in the POA with a marginal increase in the GFAP level from the ME-ARC region. These results demonstrate the involvement of synaptic proteins in the dynamic plasticity of the ME-ARC region of hypothalamus, allowing GnRH nerve terminals to release the neurohormone into the pituitary portal blood on the day of proestrous.
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PMID:Neuroendocrine plasticity in GnRH release during rat estrous cycle: correlation with molecular markers of synaptic remodeling. 1239 29

Cerebrospinal fluid-contacting neurons (CSFcNs) occur in various brain regions of lower vertebrates. In mammals, they are restricted to medullospinal areas, and little is known about their projection sites. In the present work, we investigated some morphofunctional characteristics of such neurons in the rat spinal cord by light and electron microscopic immunocytochemistry. CSFcNs expressing the P2X(2) subunit of purinergic receptors were present throughout the spinal cord, though more numerous at lower thoracolumbar and sacral levels. These neurons coexpressed GAD and the polysialylated neural cell adhesion molecule (PSA-NCAM), a marker of cellular plasticity. From low thoracic levels downward, tiny amyelinic axons (less than 200 nm in diameter) were tightly packed in bundles, which ran along the ependyma and extended ventrally, eventually concentrating against the walls of the ventral median fissure. In addition to P2X(2), GAD, gamma-aminobutyric acid (GABA), and PSA, these axons expressed GAP-43 immunoreactivity. Moreover, they were labelled along their entire lengths with antibodies against synaptotagmin and synaptophysin, but these failed to reveal intraspinal terminal fields. Taken together, our observations indicate the presence in the rat spinal cord of a highly plastic system of GABAergic CSFcNs that express the P2X(2) subunit of purinergic receptors. The function of this original system remains open to question. In these neurons, the P2X(2) receptors may confer a sensitivity to ATP either present in the CSF or released by nearby neurons of the central autonomic area.
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PMID:Cerebrospinal fluid-contacting neurons in the rat spinal cord, a gamma-aminobutyric acidergic system expressing the P2X2 subunit of purinergic receptors, PSA-NCAM, and GAP-43 immunoreactivities: light and electron microscopic study. 1254 16

Perinatal administration of the N-methyl-Dd-aspartate (NMDA) receptor antagonist phencyclidine (PCP) has been reported to produce regionally selective apoptotic cell death in the frontal cortex. The development of certain behavioral abnormalities following PCP treatment suggested that extracortical regions such as the striatum also could be affected. In this study, perinatal PCP treatment caused a marked reduction in striatal, but not hippocampal, staining for polysialic acid-neural cell adhesion molecule (PSA-NCAM), an NMDA-regulated molecule important in synaptogenesis. In order to isolate striatal influences to the cortex, this investigation was continued in vitro using corticostriatal slices. For these experiments we cultured coronal corticostriatal slices from postnatal day 7 rats. After 4 days in vitro, PCP was added for 48 h and then washed out for 24 h before harvesting the tissue. Similar to what was observed in vivo, we found that PCP treatment results in a marked reduction in striatal staining for PSA-NCAM. No change was observed in the mature form of NCAM. In striatal synaptoneurosomes, immunoblot analysis confirmed that the levels of PSA-NCAM and synaptophysin, a molecule often used as a marker of synaptogenesis, were substantially down-regulated by PCP. These effects were prevented by M40403, a superoxide dismutase mimetic that also prevented the PCP-induced terminal dUTP nick-end labeling of DNA fragments that was observed selectively in the cortex. These data suggest that PCP causes cell death by apoptosis selectively in the cortex, but not in the striatum, following either in vivo treatment of perinatal rat pups or in vitro treatment of corticostriatal slices. Further, cortical apoptosis induced by PCP negatively impacts striatal synaptogenesis, a process important in normal neural development. This deficit is probably caused by a reduction in corticostriatal neurotransmission. It is possible that the dysregulation of striatal synaptogenesis contributes to the behavioral abnormalities observed following perinatal PCP administration in vivo.
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PMID:Blockade of N-methyl-D-aspartate receptors by phencyclidine causes the loss of corticostriatal neurons. 1506 89

Small cell prostatic carcinoma is rare, with a poor prognosis. The authors report a case of small cell prostatic carcinoma in a 30-year-old patient diagnosed at the stage of metastases. Immunohistochemistry showed positive anti-neuron-specific enolase (NSE.) and anti-synaptophysin antibodies, while serum PSA was normal (1.2 ng/ml). The patient was treated by cisplatin-etoposide combination chemotherapy, but died 20 days after the first course.
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PMID:[Small cell prostatic carcinoma detected at the stage of metastases]. 1577 11

The rat medial prefrontal cortex, an area considered homologous to the human prefrontal cortex, is a region in which neuronal structural plasticity has been described during adulthood. Some plastic processes such as neurite outgrowth and synaptogenesis are known to be regulated by the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). Since PSA-NCAM is present in regions of the adult CNS which are undergoing structural remodeling, such as the hypothalamus or the hippocampus, we have analyzed the expression of this molecule in the medial prefrontal cortex of adult rats using immunohistochemistry. PSA-NCAM immunoreactivity was found both in cell bodies and in the neuropil of the three divisions of the medial prefrontal cortex. All cell somata expressing PSA-NCAM corresponded to neurons and 5' bromodeoxyuridine labeling after long survival times demonstrated that these neurons were not recently generated. Many of these PSA-NCAM immunoreactive neurons in the medial prefrontal cortex could be classified as interneurons on the basis of their morphology and glutamate decarboxylase, isoform 67 expression. Some of the PSA-NCAM immunoreactive neurons also expressed somatostatin, neuropeptide Y and calbindin-D28K. By contrast, pyramidal neurons in this cortical region did not appear to express PSA-NCAM. However, some of these principal neurons appeared surrounded by PSA-NCAM immunoreactive puncta. Some of these puncta co-expressed synaptophysin, suggesting the presence of synapses. Since the etiology of some psychiatric disorders has been related to alterations in medial prefrontal cortex structural plasticity, the study of PSA-NCAM expression in this region may open a new approach to the pathophysiology of these mental disorders.
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PMID:PSA-NCAM expression in the rat medial prefrontal cortex. 1621 31

Hippocampus dentate gyrus (DG) is characterized by neuronal plasticity processes in adulthood, and polysialylation of NCAM promotes neuronal plasticity. In previous investigations we found that alpha-tocopherol increased the PSA-NCAM-positive granule cell number in adult rat DG, suggesting that alpha-tocopherol may enhance neuronal plasticity. To verify this hypothesis, in the present study, structural remodeling in adult rat DG was investigated under alpha-tocopherol supplementation conditions. PSA-NCAM expression was evaluated by Western blotting, evaluation of PSA-NCAM-positive granule cell density, and morphometric analysis of PSA-NCAM-positive processes. In addition, the optical density of synaptophysin immunoreactivity and the synaptic profile density, examined by electron microscopy, were evaluated. Moreover, considering that PSA-NCAM expression has been found to be related to PKCdelta activity and alpha-tocopherol has been shown to inhibit PKC activity in vitro, Western blotting and immunohistochemistry followed by densitometry were used to analyze PKC. Our results demonstrated that an increase in PSA-NCAM expression and optical density of DG molecular layer synaptophysin immunoreactivity occurred in alpha-tocopherol-treated rats. Electron microscopy analysis showed that the increase in synaptophysin expression was related to an increase in synaptic profile density. In addition, Western blotting revealed a decrease in phospho-PKC Pan and phospho-PKCdelta, demonstrating that alpha-tocopherol is also able to inhibit PKC activity in vivo. Likewise, immunoreactivity for the active form of PKCdelta was lower in alpha-tocopherol-treated rats than in controls, while no changes were found in PKCdelta expression. These results demonstrate that alpha-tocopherol is an exogenous factor affecting neuronal plasticity in adult rat DG, possibly through PKCdelta inhibition.
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PMID:alpha-Tocopherol affects neuronal plasticity in adult rat dentate gyrus: the possible role of PKCdelta. 1667 95

Structural modifications occur in the brain of severely depressed patients and they can be reversed by antidepressant treatment. Some of these changes do not occur in the same direction in different regions, such as the medial prefrontal cortex, the hippocampus or the amygdala. Differential structural plasticity also occurs in animal models of depression and it is also prevented by antidepressants. In order to know whether chronic fluoxetine treatment induces differential neuronal structural plasticity in rats, we have analyzed the expression of synaptophysin, a protein considered a marker of synaptic density, and the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a molecule involved in neurite and synaptic remodeling. Chronic fluoxetine treatment increases synaptophysin and PSA-NCAM expression in the medial prefrontal cortex and decreases them in the amygdala. The expression of these molecules is also affected in the entorhinal, the visual and the somatosensory cortices.
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PMID:Chronic antidepressant treatment induces contrasting patterns of synaptophysin and PSA-NCAM expression in different regions of the adult rat telencephalon. 1730 40

We report two cases of combined small-cell carcinoma (SCC) and adenocarcinoma of prostate. Case 1 was a 76-year-old man with loss of appetite and body weight and neck lymphadenopathies. Whole body computed tomography (CT) revealed prostatic swelling, pancreatic mass, para-aortic lymphadenopathies, and multiple lung nodules. Elevation of tumor markers (prostate specific antigen [PSA, 1,760 ng/ml] and neuron-specific enolase [NSE, 88 ng/ml]) was noted. Needle biopsy of the prostate demonstrated both SCC and adenocarcinoma. Only within the part of SCC, were neuroendocrine (NE) markers (chromogranin A [CgA], NCAM, and synaptophysin [SNP]) expressed. Maximum androgen blockade (MAB) resulted in a decrease of PSA (5.13 ng/ml) but an increase of NSE (810 ng/ml). Cytotoxic chemotherapy was not possible because of his poor performance state and renal dysfunction. The patient died three months after the diagnosis. Case 2 was a 69-year-old male with dysuria. The symptom and elevated serum PSA (23.1 ng/ml) prompted prostatic needle biopsy, which demonstrated combined SCC/adenocarcinoma. NE markers (CgA and SNP) were weakly expressed in the part of SCC. Serum NSE was 6.9 ng/ml. After MAB, serum PSA dropped to the normal range (0.192 ng/ml) and the effect of MAB was judged as complete response (CR). The patient has been alive for 15 months with no signs of relapse. Treatment of combined SCC and adenocarcinoma of prostate poses a dilemma. In Case 1, MAB was effective for adenocarcinoma but not for SCC. The opposite situation would be expected with systemic chemotherapy. However, the histologically similar Case 2 achieved CR with MAB alone. Much remains to be elucidated to better manage combined SCC/adenocarcinoma of prostate.
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PMID:[Combined small-cell carcinoma/adenocarcinoma of prostate: report of two cases]. 1770 84

A "neuroplastic" hypothesis proposes that changes in neuronal structural plasticity may underlie the aetiology of depression and the action of antidepressants. The medial prefrontal cortex (mPFC) is affected by this disorder and shows an intense expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-associated molecule, which is expressed mainly in interneurons. The monoamines serotonin, dopamine and noradrenaline are the principal targets of antidepressant action. Pharmacological manipulation of serotonin levels regulates synaptophysin and PSA-NCAM expression in the adult mPFC. However, the involvement of structural plasticity on the antidepressant effects of dopamine has not been well explored yet. Using immunohistochemistry, we have studied the relationship between dopaminergic fibers and PSA-NCAM expressing neurons in the mPFC and the expression of D2 receptors. In order to evaluate the effects of dopamine in neuronal structural plasticity and on inhibitory neurotransmission, we have analyzed the expression of synaptophysin, PSA-NCAM and GAD67 in the mPFC after cortical dopamine depletion with 6-OHDA and after chronic treatments with the D2 receptor antagonist haloperidol or the D2 receptor agonist PPHT. Many dopaminergic fibers were observed in close apposition to PSA-NCAM expressing neurons and 76% of these cells co-expressed D2 receptor. Both haloperidol treatment and 6-OHDA injection reduced significantly PSA-NCAM, synaptophysin and GAD67 expression in the mPFC. Conversely, PPHT treatment increased the expression of these molecules. Our results give support to the "neuroplastic" hypothesis of depression, suggesting that dopamine acting on D2 receptors may modulate neuronal structural plasticity and inhibitory neurotransmission through changes in PSA-NCAM expression.
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PMID:Dopamine acting through D2 receptors modulates the expression of PSA-NCAM, a molecule related to neuronal structural plasticity, in the medial prefrontal cortex of adult rats. 1871 70


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