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J Simon

Publications and source records attributed to J Simon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Nucleotide receptors in the nervous system. An abundant component using diverse transduction mechanisms.

Extracellular nucleotides achieve their role as cell-to-cell communicators by acting at cell surface transmembrane receptors-the P2 receptors. Before molecular cloning led to the isolation of any P2-receptor sequence, a small number of receptor types had been proposed on the basis of pharmacological evidence. The application of molecular biology to this field of receptor research has indicated that a great underestimation of the number of receptor subtypes and of their abundance had occurred. There are now known to be seven characterized P2Y (G protein linked) receptors and the same number again of P2X receptors of the transmitter-gated ion channel type. In this review, we discuss the properties of these cloned receptors, their distribution within the nervous system, and their methods of signal transduction.

Adenosine Triphosphate↗
PubMed1997

Distribution of [35S]dATP alpha S binding sites in the adult rat neuraxis.

Highly abundant, saturable and specific binding sites for [35S]2'-deoxyadenosine 5'-O-(1-thio) triphosphate ([35S]dATP alpha S, Kd: 9 +/- 2 nM; Bmax: 39 +/- 8 pmol/mg protein) are present in adult rat brain membranes and have characteristics consistent with those expected for a P2Y1 receptor. The anatomical distribution of these binding sites in the brain and spinal cord was examined using in vitro autoradiography. The [35S]dATP alpha S binding sites showed a widespread distribution throughout the brain and spinal cord. They could be displaced by a large excess (100 microM) of 2-methylthioATP (2MeS-ATP) but not by uridine-5'-triphosphate (UTP) or alpha,beta-methyleneATP (alpha,beta-meATP). Within the cortical regions labelling was of equal medium density. However, discrete structures and nuclei within the olfactory bulb, subcortical telencephalon, hippocampal complex, thalamic regions and mesencephalon displayed a variety of densities. Within the spinal cord, gray matter was labelled at a greater density than the funiculi. The present study clarifies the anatomical distribution of P2Y1 and closely related receptors within the central nervous system of rat and extends the evidence that those receptors are abundant and widely distributed within the neuraxis.

Animals↗
PubMed1997

Affinity labelling of frog brain opioid receptors by dynorphin(1-10) chloromethyl ketone.

It has been previously found that chloromethyl ketone derivatives of enkephalins bind irreversibly to the opioid receptors in vitro. Recently a novel affinity reagent, Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Gly chloromethyl ketone (Dynorphin(1-10)-Gly11 chloromethyl ketone, DynCMK) was synthesized, and its binding characteristics to frog (Rana esculenta) brain membranes were evaluated. In competition experiments, the product shows a relatively high affinity for the kappa-opioid binding sites labelled by [3H]ethylketocyclazocine (Ki is approximately equal to 200 nM), whereas its binding to the 1 ([3H]dihydromorphine) and to the delta sites ([3H]D-Ala2-Leu5]enkephalin) is weaker. Preincubation of the frog brain membranes with DynCMK at micromolar concentrations results in a washing-resistant and dose-dependent inhibition of the [3H]ethylketocyclazocine binding sites. Saturation binding analysis of the membranes preincubated with 50 microM DynCMK reveals a significant decrease in the number of specific binding sites for [3H]ethylketocyclazocine compared to the control values. The kappa-preferring binding properties of the compound suggest that it could serve as an affinity label for the kappa-type of opioid receptors.

Affinity Labels↗
PubMed1997

Differential diagnosis of hot flashes.

OBJECTIVE: The purpose of this study is to present the physiology and differential diagnosis of hot flashes, other than associated with menopause, in order to facilitate the proper evaluation of symptomatic patients with hot flashes. STUDY DESIGN: Literature search using Med-Line computer access. RESULTS: Interest in flushing reaction began in historic times. With the rapidly expanding population of women over the age of 45 and prevalence of hot flashes as menopausal symptoms, physicians need to be aware of other medical conditions which may mimic hot flashes. These include flushing due to systemic diseases, carcinoid syndrome, systemic mast cell disease, pheochromocytoma, medullary carcinoma of the thyroid, pancreatic islet-cell tumors, renal cell carcinoma, neurological flushing, emotional flushing, spinal cord injury, flushing reaction related to alcohol and drugs, flushing associated with food additives and eating. CONCLUSION: There is a wide variety of disease processes that can cause hot flashes. Knowledge of the nature of these disease processes is necessary for quick recognition of patients with hot flashes who do not respond to estrogen replacement treatment, and to facilitate the proper evaluation of atypical patients.

Body Temperature Regulation↗
PubMed1997

Humoral response against heat shock proteins and other mycobacterial antigens after intravesical treatment with bacille Calmette-Guérin (BCG) in patients with superficial bladder cancer.

Few studies have analysed the antibody response during intravesical BCG immunotherapy for superficial bladder cancer. We have examined the evolution in serum antibody response against several heat shock proteins (hsp), including the recombinant mycobacterial hsp65 and the native protein P64 from BCG, GroEL from Escherichia coli (hsp60 family), recombinant mycobacterial hsp70 and the E. coli DnaK (hsp70 family), against purified protein derivative of tuberculin (PPD) and the AG85 complex of Mycobacterium bovis BCG, as well as against tetanus toxoid in 42 patients with a superficial bladder tumour, 28 treated with six intravesical BCG instillations and 14 patients used as controls. We also analysed the lymphoproliferative response of peripheral blood mononuclear cells against PPD in this population. Data of antibody responses at 6 weeks post BCG were available in all 28 patients, and at 4 month follow up in 17 patients. All patients who demonstrated a significant increase in IgG antibodies against PPD at 4 months follow up had a significant increase already at 6 weeks of follow up. In contrast, IgG antibodies against hsp increased significantly from 6 weeks to 4 months post-treatment. A significant increase in IgG antibodies against PPD, hsp65, P64, GroEL, and hsp70 at 4 months follow up was observed in 10/17, 8/17, 10/17, 4/17 and 8/17 patients. Native P64 protein elicited a higher antibody response than recombinant mycobacterial hsp65. No increase in antibody response was observed against Dnak from E. coli, against AG85 or tetanus toxoid after BCG therapy. An increase in IgG antibodies against P64 at 4 months follow up compared with pretreatment values was found to be a significant predictor of tumour recurrence (P<0.01). Further studies with a larger number of patients are needed to confirm the value of the antibody response against P64 as a clinical independent prognostic factor.

Administration, Intravesical↗
PubMed1997

Localization and functional expression of splice variants of the P2X2 receptor.

cDNAs encoding three splice variants of the P2X2 receptor were isolated from rat cerebellum. The first variant has a serine/proline-rich segment deleted from the intracellularly located carboxyl-terminal domain of the P2X2 subunit. The second and third variants have the splice site in the second half of the predicted first transmembrane domain. Either a 12-amino acid insertion or a six-amino acid deletion occurs at this position. cRNAs for these isoforms of the P2X2 subunit were injected into Xenopus laevis oocytes and tested for function. ATP evoked inward currents only with the splice variant [designated P2X2(b)] having the 69-amino acid deletion. The potencies of various agonists at the homomeric P2X2(b) receptor were not significantly different from those at the P2X2(a) homomeric channel. However, the P2X2(b) receptor showed significantly lower antagonist sensitivity. In contrast to the nondesensitizing P2X2(a) receptor, prolonged application of ATP produced a more rapid desensitization of the P2X2(b) receptor. When the P2X2(a) and P2X2(b) receptor responses were recorded in transfected mammalian cells, this difference was again found. The change in desensitization may be determined by proline/serine-rich segments and/or phosphorylation motifs that are removed from the tail region in formation of the P2X2(b) subunit. In situ hybridization of the three newly isolated isoforms of the P2X2 subunit was performed at the macroscopic and cellular levels; transcripts for two of them [P2X2(b) and p2x2(c)] but not the third [p2x2(d)], which carries the 12-amino acid addition, were present in many structures in the neonatal rat brain and on sensory and sympathetic ganglia. mRNA for the p2x2(d) splice variant was present only in the nodose ganglion, at a low level.

Adenosine Triphosphate↗
PubMed1997

Evolutionary conservation and predicted structure of the Drosophila extra sex combs repressor protein.

The Drosophila extra sex combs (esc) protein, a member of the Polycomb group (PcG), is a transcriptional repressor of homeotic genes. Genetic studies have shown that esc protein is required in early embryos at about the time that other PcG proteins become engaged in homeotic gene repression. The esc protein consists primarily of multiple copies of the WD repeat, a motif that has been implicated in protein-protein interaction. To further investigate the domain organization of esc protein, we have isolated and characterized esc homologs from divergent insect species. We report that esc protein is highly conserved in housefly (72% identical to Drosophila esc), butterfly (55% identical), and grasshopper (56% identical). We show that the butterfly homolog provides esc function in Drosophila, indicating that the sequence similarities reflect functional conservation. Homology modeling using the crystal structure of another WD repeat protein, the G-protein beta-subunit, predicts that esc protein adopts a beta-propeller structure. The sequence comparisons and modeling suggest that there are seven WD repeats in esc protein which together form a seven-bladed beta-propeller. We locate the conserved regions in esc protein with respect to this predicted structure. Site-directed mutagenesis of specific loops, predicted to extend from the propeller surface, identifies conserved parts of esc protein required for function in vivo. We suggest that these regions might mediate physical interaction with esc partner proteins.

Amino Acid Sequence↗
PubMed1997

A domain shared by the Polycomb group proteins Scm and ph mediates heterotypic and homotypic interactions.

The Sex comb on midleg (Scm) and polyhomeotic (ph) proteins are members of the Polycomb group (PcG) of transcriptional repressors. PcG proteins maintain differential patterns of homeotic gene expression during development in Drosophila flies. The Scm and ph proteins share a homology domain with 38% identity over a length of 65 amino acids, termed the SPM domain, that is located at their respective C termini. Using the yeast two-hybrid system and in vitro protein-binding assays, we show that the SPM domain mediates direct interaction between Scm and ph. Binding studies with isolated SPM domains from Scm and ph show that the domain is sufficient for these protein interactions. These studies also show that the Scm-ph and Scm-Scm domain interactions are much stronger than the ph-ph domain interaction, indicating that the isolated domain has intrinsic binding specificity determinants. Analysis of site-directed point mutations identifies residues that are important for SPM domain function. These binding properties, predicted alpha-helical secondary structure, and conservation of hydrophobic residues prompt comparisons of the SPM domain to the helix-loop-helix and leucine zipper domains used for homotypic and heterotypic protein interactions in other transcriptional regulators. In addition to in vitro studies, we show colocalization of the Scm and ph proteins at polytene chromosome sites in vivo. We discuss the possible roles of the SPM domain in the assembly or function of molecular complexes of PcG proteins.

Amino Acid Sequence↗
PubMed1997

Sex-specific expression of Heschl's gyrus functional and structural abnormalities in paranoid schizophrenia.

OBJECTIVE: Evidence supports abnormal temporal lobe structure and function in schizophrenia. Some abnormalities, particularly involving the auditory cortex, appear to be sex specific. These findings were extended to anatomical and physiological descriptors. METHOD: The authors quantified the volume, surface area, and three-dimensional location of Heschl's gyri on magnetic resonance imaging (MRI) images of 21 patients with paranoid schizophrenia and 24 healthy comparison subjects. Neuromagnetic localizations of the 100-msec latency auditory evoked field (M100) were compared with MRI-determined locations of Heschl's gyri, computed as the geometric center of mass of the volume. RESULTS: Volumetric measures revealed small Heschl's gyri only in male patients. Asymmetry was found in the location of the Heschl's gyrus centroid (more anterior on the right) across all groups. Male comparison subjects had M100 locations posterior to the Heschl's gyrus centroid in the left hemisphere and close to the Heschl's gyrus centroid on the right, while male patients had M100 sources anterior to the Heschl's gyrus centroid on the left. All women had M100 locations posterior to the Heschl's gyrus centroid on the left and anterior to it on the right. CONCLUSIONS: These results demonstrate that some temporal lobe abnormalities in schizophrenia are sex specific. They also suggest that the anomalous lateralization of the auditory evoked field cannot be explained by a shift in the underlying anatomy, since the anatomical substrate is lateralized in both comparison subjects and patients of both sexes. These findings may indicate a sex-specific functional reorganization in the auditory cortex in schizophrenia.

Adult↗
PubMed1997

Effects of a duodenal glucose infusion on the relationship between plasma concentrations of glucose and insulin in dairy cows.

The effects of duodenal infusion of glucose on the relationship between plasma concentrations of glucose and insulin and on milk composition were investigated in a crossover design. Eight dairy cows were continually infused with water (control) or glucose (1.5 kg/d). Cows received diets consisting of dehydrated whole-plant maize in restricted amounts to equalize the energy supply between treatments. Basal (before meal) plasma concentrations of glucose and insulin were increased, but concentrations of nonesterified fatty acids (NEFA) were decreased, by glucose treatment. During the first 2 h after feed distribution, plasma insulin increased, and plasma glucose and NEFA decreased, in both control and treated cows. Afterward, plasma glucose increased in treated cows but further decreased in control cows. The difference reached 8 mg/100 ml without any change in plasma insulin. During the meal, concentrations of growth hormones in plasma were inhibited to a similar extent in both groups. In response to intravenous glucose or insulin challenges, changes in plasma glucose, NEFA, and insulin stimulated by glucose were also very similar in both groups. In conclusion, duodenal infusion of glucose increased basal plasma concentrations of glucose and insulin, increased postprandial plasma glucose, and decreased NEFA without inducing insulin resistance. Glucose treatment did not change milk yield but decreased milk fat yield, mainly through a decrease in the yield of C18 fatty acids that were derived from circulating fatty acids. In the absence of insulin resistance, the decrease in the yield of C18 fatty acids might be attributed to an inhibition of adipose lipolysis or an increase in adipose lipogenesis.

3-Hydroxybutyric Acid↗
PubMed1997

Evolution and clinical significance of the T cell proliferative and cytokine response directed against the fibronectin binding antigen 85 complex of bacillus Calmette-Guerin during intravesical treatment of superficial bladder cancer.

PURPOSE: The antitumorigenic effect of intravesical bacillus Calmette-Guerin (BCG) in superficial bladder cancer was reported to be initiated by the attachment of BCG to the bladder wall via fibronectin. The antigen 85 complex secreted in BCG culture filtrate binds specifically to fibronectin and is a powerful T cell stimulus. Therefore, we investigated the evolution and clinical significance of the cellular proliferative response and cytokine production during intravesical BCG therapy against this purified antigen 85 complex. MATERIALS AND METHODS: Evolution of the lymphoproliferation, interleukin-2 and interferon-gamma production of peripheral blood lymphocytes against tuberculin (purified protein derivative), purified antigen 85, BCG culture filtrate, whole BCG bacilli and pokeweed mitogen was tested before and after 6 weekly intravesical BCG instillations in 29 patients with superficial bladder cancer at intermediate or high risk for recurrence. RESULTS: A major increase in the lymphoproliferative response against purified protein derivative, antigen 85, BCG culture filtrate, whole BCG and pokeweed mitogen was observed in 69.0, 65.5, 79.3, 48.3 and 65.3% of the patients, respectively, analyzed after BCG therapy. Reactivity returned to baseline values at 6 months of followup. Of the patients who received a second BCG course because of tumor recurrence 66% had a novel increase in lymphoproliferation against antigen 85. An increase in the production of interleukin-2 and interferon-gamma by peripheral lymphocytes against antigen 85 was noted in 42.1 and 50% of the treated patients, respectively, after a single BCG course. During a mean followup of 23.11 months 48.5% of the patients remained tumor-free. No correlation could be found between the immunological response against any of the BCG antigens and the clinical evolution of the response. CONCLUSIONS: Intravesical BCG instillations induce a transient (less than 6 months) peripheral immune activation against several purified BCG antigens and among them the fibronectin binding antigen 85 complex. Reactivation is observed in most cases after additional BCG courses. The absence of long lasting immune activation after a single 6-week course of BCG could be related to the increased clinical efficacy observed with BCG maintenance instillations.

Administration, Intravesical↗
PubMed1997

Prevalence of anaemia in semi-urban areas of Peshawar, Pakistan: a challenge for health professionals and policy makers.

Iron deficiency anaemia is a serious problem among Pakistani children. Pre-intervention haematological status of children under two years was assessed as part of a double-blind, randomized controlled community-based study conducted in two semi-urban areas of Peshawar. The primary objective was to assess the impact of iron deficiency anaemia and iron intervention on growth and morbidity. Three hundred and twenty children who met the criteria of a "healthy child" were recruited for the study. Blood samples were drawn from 275 children for haemoglobin (Hb) and serum ferritin (SF) analyses. The children were classified as anaemic (Hb < 11 g/dl); iron deficient (SF < 12 ng/ml) and iron deficient anaemic (Hb < 11 g/dl and SF < 12 ng/ml). Ninety percent of the children were anaemic, 67% iron deficient and 63% iron deficient anaemic. Anaemia was more prevalent in boys who had significantly lower Hb and SF values than girls. The magnitude of anaemia in these children tended to increase with age. The study demonstrates that iron deficiency is the predominant cause of anaemia (69%) in children under two years. Minimization of iron deficiency anaemia should be a public health priority in order to prevent suffering of children and avert the associated cognitive and physical deficits in child development.

Anemia, Iron-Deficiency↗
PubMed1997

Immunoscintigraphy with anti-225.28S for ocular melanoma--a comparison with histology and immunohistochemistry.

AIM: The purpose of this prospective study was to evaluate the value of immunoscintigraphy (ISG) with anti-225.28S in clinically suspected ocular melanoma. METHODS: For this purpose standardized ISG was performed in 36 patients using both planar acquisition and emission computed tomography (ECT). Ocular melanoma was present in 31 patients. In 21 patients therapy was enucleation of the eye. These specimens were evaluated by histology and immunohistochemistry in 11 of 21 patients. RESULTS: Regarding the clinical diagnosis, ISG was positive only in 15 of 31 patients with ocular melanoma, regarding histology in 11 of 21 and regarding immunohistochemistry in 5 of 6 patients with a positive immunoreaction 5 patients showed no immunoreactivity, their ISG was negative. CONCLUSION: Thus a good correlation between ISG and immunohistochemistry was observed. However ISG using the cutaneous melanoma antibody 225.28S cannot be recommended for the diagnostic work-up of an ocular melanoma considering the poor immunoreactivity.

Adult↗
PubMed1997

[The need of prolonged BCG treatment in superficial bladder cancer is suggested by the development of a peripheral immune response induced by BCG].

Optimal duration of immunotherapy treatment by BCG for the prevention of recurrences of superficial bladder cancer is still unknown. We have studied the evolution and duration of the cellular immunity response at the peripheral level after BCG intravesical instillations. Our results show that immunity activation after BCG is of short duration and don't take more than 6 months. Our results support, strengthen and partially allow to explain the utility of maintenance treatment by BCG following 6-weekly instillations.

Adjuvants, Immunologic↗
PubMed1997

Conservative management of ureteric stones.

The authors review the current conservative management of ureteric stones. The physiopathology of the renal colic is analyzed with its implications in the medical treatment. The role of NSAID is enhanced. Stone size and stone location are to be considered when evaluating the possibility of spontaneous passage of the stone. Stones less than 3 mm in diameter of the lower ureter will pass spontaneously in 90% of the cases while stones more then 6 mm in the upper ureter will not pass in most cases. The role of stone dissolution in uric acid and cystine stones is discussed. SWL is not controversial in the management of upper stones less than 15 mm in size. The authors report their experience with SWL of ureteric stones in upper, middle or lower ureteric stones with a success rate of respectively 87%, 65% and 84%.

Anti-Inflammatory Agents, Non-Steroidal↗