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Biomedical subjects

M Tal

Publications and source records attributed to M Tal.

At least 19 recordsLinked to original sources
PubMed2003

P2 receptors in satellite glial cells in trigeminal ganglia of mice.

There is strong evidence for the presence of nucleotide (P2) receptors in sensory neurons, which might play a role in the transmission of pain signals. In contrast, virtually nothing is known about P2 receptors in satellite glial cells (SGCs), which are the main glial cells in sensory ganglia. We investigated the possibility that P2 receptors exist in SGCs in murine trigeminal ganglia, using Ca(2+) imaging, patch-clamp recordings, and immunohistochemistry. We found that ATP caused an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in SGCs. As adenosine had no effect on [Ca(2+)](i), and the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid largely blocked the response to ATP we conclude that P1 receptors did not contribute to the responses. We obtained the following evidence that the responses to ATP were mediated by metabotropic P2Y receptors: (i) persistence of the responses in Ca(2+)-free solution, (ii) inhibition of the response by cyclopiazonic acid, (iii) [Ca(2+)](i) increases in response to the P2Y agonists uridine triphosphate, adenosine thiodiphosphate, and 2-methylthio ADP, and (iv) failure of the P2X agonist alpha,beta-methylene ATP to elicit a response. Agonists of P2Y(1) receptors and uridine triphosphate, an agonist at P2Y(2) and P2Y(4) receptors, induced [Ca(2+)](i) increases suggesting that at least these P2Y receptor subtypes are present on SGCs. Using an antibody against the P2Y(4) receptor, we found immunopositive SGCs. Patch-clamp recordings of SGCs did not reveal any inward current due to ATP. Therefore, there was no evidence for the activation of ionotropic P2X receptors under the present conditions. The results indicate the presence of functional nucleotide (P2Y) receptors in SGCs.

Adenosine Triphosphate↗
PubMed2002

[Gingival depigmentation for aesthetic purposes using erbium:YAG laser: rationale and technique].

Melanin, carotene and hemoglobin are the most common natural pigments contributing to the normal color of the gums. Although physiologic and ethnic melanin pigmentation is not a medical problem, complains about "black gums" are common. Gingival depigmentation has been carried out using surgical, chemical, electrosurgical and cryosurgical procedures. Recently, Laser Ablation has been recognized as one of the most effective, pleasant and reliable techniques. Effective depigmentation of the gingival requires removal of all or most of the melanocytes from the basal layer of the gingival epithelium. Using non-specific radiation means ablation of all the epithelial cell layers, as well as connective tissue rete pegs, leaving behind only remnants of the epithelial rete ridges. CO2, Nd:YAG and Erbium:YAG lasers, meeting most of these requirements and being available in the dental office, seems to be the lasers of choice for this procedure. Five patients (3 F; 2 M) who were referred to the TAUSDM for cosmetic therapy of "black gums" were treated using Erbium-YAG laser. The laser beam was set up at 850 mj/10 pulses per second producing peak power of 2.13 kwand peak power density of 30.43 kw/sq/cm. The beam was defocused to produce a 3 mm diameter circle, thus reducing the beam penetration while increasing the treated surface. Using the "brush" technique, 800-2,000 pulses were required per patient, with an average of 500-1,100 pulses per 1 sq.cm, depending on the thickness of the epithelium and the intensity of the pigmentation. Treatment required only topical anesthesia. Healing was uneventful and required no supportive therapy. Three months follow up has shown no repigmentation in any of the patients. Patients' evaluation analysis showed that the results were pleasing; no pain was experienced during lasing as well as during healing. Two patients were interupted by the lasing burning smell, which may be reduced or eliminated by operating a power suction during the procedure.

Aluminum Silicates↗
PubMed2001

Inflammation with no axonal damage of the rat saphenous nerve trunk induces ectopic discharge and mechanosensitivity in myelinated axons.

Inflammation along a nerve trunk with no frank axonal nerve damage produced by complete Freund's adjuvant (CFA) or Carrageenan is known to induce a painful peripheral neuropathy. In the present study, we examined the electrophysiological properties of myelinated axons (spontaneous discharge and mechanical sensitivity) at the inflamed nerve site. The rat saphenous nerves were exposed at mid-thigh level and wrapped in 2 mm wide bands of haemostatic oxidized cellulose (Oxycel) that were saturated with undiluted CFA. In the control rats the Oxycel) was saturated with saline. At postoperative days (PODs) 2-5 and 6-10, fine axon bundles were teased from the nerve, and electrophysiological recordings performed. At both time points spontaneous activity at the site of the application in CFA rats (PODs 2-5=9.9+/-2.5%: PODs 6-10=6.1+/-1.4%) was significantly higher than in the control animals (PODs 2-5=2.9+/-1.1%: PODs 6-10=1.6+/-1.4%: P=0.03, P=0.02, respectively). Mechanical sensitivity at both time points was significantly higher in CFA rats (PODs 2-5=12.6+/-3.1%: PODs 6-10=10.3+/-3.1%) than in saline rats (PODs 2-5=3.4+/-2.91%: PODs 6-10=0.8+/-1.0%: P=0.03, P=0.04, respectively). This study clearly shows that perineural inflammation with no axonal nerve damage induced by CFA application around the nerve trunk elevates spontaneous activity and induces mechanosensitivity in myelinated axons.

Action Potentials↗
PubMed2001

No sympathetic nerve sprouting in rat trigeminal ganglion following painful and non-painful infraorbital nerve neuropathy.

Following sciatic nerve injury sympathetic invasion and basket formation is seen in dorsal root ganglia. We examined whether this phenomenon occurs in trigeminal ganglion (TG) following axotomy (IOAx) or chronic constriction injury to the infraorbital nerve (IOCCI). The IOCCI rats developed hyperresponsiveness to pinprick stimulation consistent with this model and the IOAx rats remained hyporesponsive for most of the study period. Immunocytochemistry employing antibodies to tyrosine hydroxylase showed no sympathetic invasion or basket formation 2 and 7 weeks post surgery. This study confirms previous work that found no sympathetic invasion of TG following injury, and shows that this finding is unaffected by the presence or absence of nerve injury induced hyperresponsiveness.

Animals↗
PubMed2000

Transient action of the endothelial constitutive nitric oxide synthase (ecNOS) mediates the development of thermal hypersensitivity following peripheral nerve injury.

Neuropathic pain is a disabling feature of peripheral nerve injury. Following injury, local inflammation and the release of mediators may contribute to ectopic mechanosensitivity of the nerve-trunk and pain hypersensitivity. In the present study we investigated whether nitric oxide (NO) action and local nitric oxide synthase (NOS) expression play a role in pain hypersensitivity and A fibre-mediated ectopic hyperexcitability following a chronic constriction injury to a rat sciatic nerve. Using immunohistochemical methods we provide evidence for a unique endothelial constitutive nitric oxide synthase (ecNOS) immunoreactivity localized in early axonal endbulb-like structures of injured peripheral nerve axons. Moreover, we show that following nerve injury there is increased ecNOS-mRNA expression within the lumbar sympathetic ganglia, and that axoplasmic transport in sympathetic and other axons rather than local non-neural synthesis accounts for its accumulation in nerve fibres. We also demonstrate here that local inhibition of NOS action with the broad-spectrum inhibitor NG-nitro-L-arginine-methyl ester (L-NAME), but not more specific inhibitors of other NOS isoforms, has stereospecific, dose- and time-dependent analgesic effects that were reversed by local administration of L-arginine, the natural precursor of NO. In further work, using a teased fibre preparation, we show that administration of L-NAME, but not D-NAME, to the injury site also blocks ectopic mechanosensitivity of injured A-fibres. Our results indicate that an early and transient local ecNOS expression within early axonal endbulb-like structures, some arising from sympathetic axons, plays a critical role in the development of neuropathic pain.

Animals↗
PubMed1999

Myelinated afferent fiber types that become spontaneously active and mechanosensitive following nerve transection in the rat.

It is difficult to know which afferent types preferentially develop ectopic firing characteristics following nerve injury because axotomy disconnects the sensory receptor ending from the remainder of the afferent neuron. We compared the prevalence of ectopic firing originating in nerve-end neuromas of nerves serving muscle and skin in the rat. Spontaneous firing was much more prevalent in the injured medial gastrocnemius nerve, a hindlimb muscle nerve, than in the saphenous and sural nerves which primarily innervate hindlimb skin. Ectopic mechanosensitivity, on the other hand, was more prominent in neuromas of the cutaneous nerves. In neuromas of the facial nerve, a cranial nerve which serves striated muscles of the face, there was no spontaneous discharge and very little ectopic mechanosensitivity. We conclude that the development of spontaneous ectopic discharge and ectopic mechanosensitivity depends on the type of myelinated afferent fiber involved.

Action Potentials↗
PubMed1999

A Role for Inflammation in Chronic Pain.

Recent studies indicate that inflammatory events induced by nerve injury play a central role in the pathogenesis of neuropathic pain. These involve inflammatory cells (eg, macrophages), the production of molecules that mediate inflammation (cytokines/interleukins), and the production of nerve growth factor (NGF). However, in many instances, neuropathic pain is associated with nerve inflammation, neuritis, in the absence of nerve injury. Studies on the role of cytokines in neuropathic pain have only recently begun, mostly in model systems that involve nerve injury. Little is known about the role of inflammation in neuropathic pain in the absence of nerve injury. We developed an animal model to study neuropathic pain and underlying inflammatory mechanisms in a system in which neuropathic pain is induced by nerve inflammation in the absence of injury, neuritis. Neuritis is provoked by local application of complete Freund's adjuvant (CFA) on the sciatic nerve. The following events in the course of experimental neuritis are described: 1) the time course of neuropathic pain, 2) the structural changes in axons and myelin, and 3) the spontaneous electrical activity (peripheral sensitization). It is conceivable that biochemical and physiologic changes (inflammatory mediators) that occur along the "pain pathway" (nociceptors, peripheral nerve, dorsal root ganglion ), dorsal root, neurons in the spinal cord) may sensitize one or all these sites along the pain pathway and hence lead to chronic pain).

Journal Article↗
PubMed1998

DNA unwinding in the CYC1 and DED1 yeast promoters.

The capacity of promoter DNA of two yeast genes to be unwound was studied. Both promoters, those of the CYC1 and DED1 genes, contain long oligopurine.oligopyrimidine (R.Y) tracts. The two promoters were cloned into negatively supercoiled plasmids, and their sensitivity to single-strand specific nuclease P1 was examined. Extensive P1 cleavage was located within the R.Y tracts, and cleavage sites were mapped. The extent of cleavage was only slightly dependent on P1 concentration, indicating a slow conversion of an intermediate form of DNA into the P1 reactive state. The cleavage required negative supercoiling and was suppressed by NaCl, MgCl2 and spermine. Two-dimensional topoisomer analysis showed that six superhelical turns were opened in the plasmids examined. The results indicate that at sufficient torsional stress, the R.Y tracts can intermittently undergo a transition into an unwound, ready-to-separate state. The oligopurine.oligopyrimidine tracts may thus serve as DNA unwinding centers in the gene promoters where they reside.

Base Sequence↗
PubMed1997

Local injection of nerve growth factor (NGF) triggers degranulation of mast cells in rat paw.

We examined the relationship between hyperalgesia and degranulation of mast cells in rats following treatment with nerve growth factor (NGF) and inflammatory mediators. Intracutaneous injection to the rat's paw of NGF (50-5000 ng, 50 microl) evoked dose-dependent thermal hyperalgesia as measured by paw withdrawal latency to noxious heat. Even more intense hyperalgesia was induced by an inflammatory mediators soup' containing BK, 5HT, PGE2 and histamine (10 microM). Counts of mast cells in the dermis were performed on coded slides under x 1000 magnification after fixation in Carnoy's solution and staining with toluidine blue. After injection of three different concentrations of NGF (50, 500, 5000 ng in 50 microl), the proportion of mast cells that were degranulated was significantly higher (P < 0.001) than after saline injection. No significant differences were found among the three concentrations of NGF. The effect of inflammatory soup on the proportion of degranulated mast cells was similar to that of NGF. These results indicate that NGF activates cutaneous mast cells and stimulates the release of inflammatory tissue mediators in the acute phase of NGF-induced hyperalgesia in the rat's paw. However, the finding that degranulation was not dose-dependent indicates that other mechanisms, independent of mast cells, are probably operating in response to NGF.

Animals↗
PubMed1997

Variability in the pattern of random amplified polymorphic DNA.

The random amplified polymorphic DNA (RAPD) technique is a simple method to detect DNA polymorphism. It is sensitive to reaction conditions. Small changes in the reactants' concentration cause variations in amplification products. Using DNA from Asparagus officinalis, Dactylis glomerata, Mercurialis annua and Escherichia coli, we examined variability in the amplification pattern associated with reaction constituents. An increase in the ratio of Taq DNA polymerase to DNA in the reaction increased the number of amplified fragments. Increasing the concentration of primer resulted in the amplification of low molecular weight DNA fragments, while lowering the concentration resulted in high molecular weight fragments. Subsets of amplified fragments required different concentrations of magnesium for their highest intensity. Mechanical shearing of DNA obtained by sonication led to reduction in amplification of a subset of products. Enzymatic fragmentation of DNA by restriction enzymes led to loss or gain of specific fragments, depending on the DNA, primer, and restriction enzyme. RAPD markers of pooled DNA of anonymous pedigree should be critically evaluated for frequent 'false positive' markers.

Base Composition↗
PubMed1996

A novel antioxidant alleviates heat hyperalgesia in rats with an experimental painful peripheral neuropathy.

Rats with an experimental painful peripheral neuropathy (the chronic injury (CCI) model) display heatevoked hyperalgesia. There is now considerable evidence that nitric oxide (NO) and nitric oxide synthase are involved in the development of hyperalgesia in acute inflammatory pain states. The mechanisms responsible for hyperalgesia in chronic pain state may involve not only NO itself, but also peroxynitrite, the product of its reaction with superoxide radical, .O2- that can lead to the formation of the free radicals .OH and NO2- Under normal metabolic conditions, the cellular enzyme super oxide dismutase (SOD) provides physiological defence against superoxide radicals. TEMPOL mimics SOD and acts as a catalyst to remove the .O2- radical. The present work shows the efficacy of a stable nitroxide radical, 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPOL), against heat-evoked hyperalgesia.

Animals↗
PubMed1996

[Amplification of protooncogenes and expression of the HER2/neu oncogene in invasive breast cancer].

The protooncogene HER2/neu was analyzed in 27 women with invasive breast cancer and in 26 with benign breast conditions. Gene amplification was found in 3 patients, 1 in stage 3 and 2 in stage 4. In 3 patients in stage 2 overexpression of protein was found. Although amplification of the gene was found to be a significant predictor of clinical outcome (p < 0.05), high expression of the gene did not correlate with prognosis. In women with benign breast conditions there were no alterations of HER2/neu amplification may become a molecular marker in some malignancies. It should be noted that since few tumors show amplification, examination of a small series may not reveal clinical association with these alterations. Therefore, our conclusions require confirmation on a larger scale with long-term clinical follow-up.

Biomarkers, Tumor↗
PubMed1995

A secretion inhibitory signal transduction molecule on mast cells is another C-type lectin.

Secretion of inflammatory mediators by rat mast cells (line RBL-2H3) was earlier shown to be inhibited upon clustering a membrane glycoprotein by monoclonal antibody G63. This glycoprotein, named mast cell function-associated antigen (MAFA), was also shown to interfere with the coupling cascade of the type 1 Fc epsilon receptor upstream to phospholipase C gamma 1 activation by protein-tyrosine kinases. Here we report that the MAFA is expressed as both a monomer and a homodimer. Expression cloning of its cDNA shows that it contains a single open reading frame, encoding a 188-amino acid-long type II integral membrane protein. The 114 C-terminal amino acids display sequence homology with the carbohydrate-binding domain of calcium-dependent animal lectins, many of which have immunological functions. The cytoplasmic tail of MAFA contains a YXXL (YSTL) motif, which is conserved among related C-type lectins and is an essential element in the immunoreceptor tyrosine-based activation motifs. Finally, changes in the MAFA tyrosyl- and seryl-phosphorylation levels are observed in response to monoclonal antibody G63 binding, antigenic stimulation, and a combination of both treatments.

Amino Acid Sequence↗
PubMed1995

A novel putative neuropeptide receptor expressed in neural tissue, including sensory epithelia.

We have used a homology based approach to identify G protein-coupled receptors preferentially expressed in retinal and taste cells. Rat and bovine sequences encoding a novel G protein-coupled receptor have been isolated. Analysis indicates that while the protein sequence is most similar to the receptors for somatostatin and opiates, it is unlikely to be a subtype of these receptors. Northern and RNase protection analysis indicates that the gene is preferentially expressed in neural and sensory tissues.

Amino Acid Sequence↗
PubMed1994

Unwound regions in yeast centromere IV DNA.

The DNA of the centromere of chromosome IV (CEN4) of Saccharomyces cerevisiae is found to be sensitive to single-strand specific nuclease P1 when inserted into a negatively supercoiled plasmid. Fine mapping identifies two P1-sensitive segments: one segment maps to essential centromere element CDEI and bordering CDEII bases, and the other segment is located in element CDEIII. The AT-rich element CDEII, which is expected to be early melting, is for the most part resistant to nuclease P1. Cleavage is inhibited by NaCl, MgCl2 and polyamines. The cleavage rate is only weakly dependent on P1 concentration in the range of 0.5 to 20 munits/microliters. The two P1-sensitive segments are also modified by the DNA-confirmation-specific reagent KMnO4. Negative superhelicity is required for all modifications. Two-dimensional topoisomer analysis indicates the unwinding of 80(+/- 10) bases within the negatively supercoiled CEN4-containing plasmid. The data best fit a model in which the DNA of the CEN4 region undergoes a transition into a paranemic intermediate in which each strand is folded into an RNA-like foldback structure.

Base Sequence↗
PubMed1994

Neuropathic pain sensations are differentially sensitive to dextrorphan.

Rats with an experimental painful peripheral neuropathy (the CCI model) display heat-hyperalgesia and mechanoallodynia. Previous work has shown that the heat-hyperalgesia is suppressed by dextrorphan (DEX) and other N-methyl-D-aspartate (NMDA) receptor antagonists. The present work shows that when tested in the same rats, a dose of DEX that is maximally effective against heat-hyperalgesia has no effect on mechano-allodynia. The results suggest that different kinds of abnormal pain sensations may be caused by different pathophysiologic mechanisms that may respond differently to drug therapy.

Animals↗
PubMed1994

The pancreatic beta-cell glucose sensor.

Pancreatic beta cells secrete insulin in response to an increase in the level of blood glucose above 5 mM, which is characteristic of the fasting state. Glucose metabolism is essential for glucose sensing, and both the high-Km glucose transporter GLUT2 and the high-Km glucose phosphorylating enzyme glucokinase have been implicated in coupling insulin secretion to extracellular glucose levels. Experiments in isolated islets, immortalized beta-cell lines and transgenic animals, together with findings in humans with maturity-onset diabetes of the young, indicate that the primary beta-cell glucose sensor is glucokinase. Although the level of GLUT2 is frequently reduced in animal models of type II diabetes, GLUT2 does not limit glucose metabolism in beta cells and does not appear to regulate glucose induction of insulin secretion.

Animals↗