Biomedical subjects

Shiv K Sharma

Publications and source records attributed to Shiv K Sharma.

At least 19 recordsLinked to original sources

PubMed2006

A tropomyosin-related kinase B ligand is required for ERK activation, long-term synaptic facilitation, and long-term memory in aplysia.

BDNF, which acts through tropomyosin-related kinase B (TrkB) receptors during mammalian development, also enhances long-term synaptic facilitation (LTF) in adult Aplysia. Because LTF is a substrate for long-term memory (LTM) in Aplysia, we examined the requirement of a secreted TrkB ligand in LTM formation at molecular, synaptic, and behavioral levels. Using an extracellular fusion protein that sequesters secreted TrkB ligands, we show that TrkB function is required for serotonin-induced activation of extracellular signal-regulated kinase, tail nerve shock-induced LTF in the CNS, and tail shock-induced LTM but is not necessary for short-term synaptic facilitation or short-term memory. These results show that a secreted growth factor, acting through a TrkB signaling cascade, is critical for the induction of long-lasting plasticity and memory formation in Aplysia.

Animals↗

PubMed2006

Ventilatory support using bilevel positive airway pressure during neuraxial blockade in a patient with severe respiratory compromise.

In pregnant patients with myasthenia gravis and respiratory compromise, neuraxial anesthesia for lower abdominal surgery can risk further respiratory depression. We report the use of epidural anesthesia for dilation and curettage and tubal ligation in a 26-yr-old woman with a 12-wk intrauterine pregnancy with severe myasthenia gravis and respiratory insufficiency in whom ventilatory support during anesthesia was provided successfully using bilevel positive airway pressure ventilation. This report demonstrates how the use of bilevel positive airway pressure for ventilatory support may improve the safety of regional anesthesia in patients with severe respiratory compromise.

Adult↗

PubMed2006

Remote Raman spectroscopic detection of minerals and organics under illuminated conditions from a distance of 10 m using a single 532 nm laser pulse.

Raman spectra of several minerals and organics were obtained from a small portable instrument at a distance of 10 m in a well-illuminated laboratory with a single 532 nm laser pulse with energy of 35 mJ/pulse. Remote Raman spectra of common minerals (dolomite, calcite, marble, barite, gypsum, quartz, anatase, fluorapatite, etc.) obtained in a short period of time (1.1 mus) clearly show Raman features that can be used as fingerprints for mineral identification. Raman features of organics (benzene, cyclohexane, 2-propanol, naphthalene, etc.) and other chemicals such as oxides, silicates, sulfates, nitrates, phosphates, and carbonates were also easily detected. The ability to identify minerals from their Raman spectra obtained from a single laser pulse has promise for future space missions where power consumption is critical. Such a system could be reduced in size by minimizing the cooling requirements for the laser unit. The remote Raman system is also capable of performing time-resolved measurements. Data indicate that further improvement in the performance of the system is possible by reducing the gate width of the detector (ICCD) from 1.1 mus to approximately 20 ns, which would significantly reduce the background signal from daylight or a well-illuminated laboratory. The 1.1 mus signal gating was effective in removing nearly all background fluorescence with 532 nm excitation, indicating that the fluorescence in most minerals is probably from long-lifetime inorganic phosphorescence.

Equipment Design↗

PubMed2005

A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers.

There has been much speculation regarding the functional relevance of G protein-coupled receptor heterodimers, primarily because demonstrating their existence in vivo has proven to be a considerable challenge. Here we show that the opioid agonist ligand 6'-guanidinonaltrindole (6'-GNTI) has the unique property of selectively activating only opioid receptor heterodimers but not homomers. Importantly, 6'-GNTI is an analgesic, thereby demonstrating that opioid receptor heterodimers are indeed functionally relevant in vivo. However, 6'-GNTI induces analgesia only when it is administered in the spinal cord but not in the brain, suggesting that the organization of heterodimers is tissue-specific. This study demonstrates a proof of concept for tissue-selective drug targeting based on G protein-coupled receptor heterodimerization. Importantly, targeting opioid heterodimers could provide an approach toward the design of analgesic drugs with reduced side effects.

Analgesics↗

PubMed2005

Raman efficiencies of natural rocks and minerals: performance of a remote Raman system for planetary exploration at a distance of 10 meters.

Raman spectroscopy is a powerful technique for materials analysis, and we are developing and analyzing a remote Raman system for use on a planetary lander or rover. We have acquired data at a distance of 10m from a variety of geologic materials using different instrument designs. We have employed a pulsed laser with both an ungated detector and a gated detector. A gated detector can reduce long-lived fluorescence while still collecting all Raman signal. In order to design a flight instrument, we need to quantify how natural surfaces will respond to laser stimulus. We define remote Raman efficiency of natural surfaces as the ratio of radiant exitance leaving a natural surface to the irradiance of the incident laser. The radiant exitance of a natural surface is the product of the sample radiance, the projected solid angle, and the full-width-half-maximum of the Raman signal. We have determined the remote Raman efficiency for a variety of rocks and minerals. The best efficiencies are achieved for large, clear, single crystals that produce the most radiant exitance, while darker fine-grained mineral mixtures produce lower efficiencies. By implementing a pulsed laser, gated detector system we have improved the signal detection and have generally decreased the integration time necessary to detect Raman signal from natural surfaces.

Data Interpretation, Statistical↗

PubMed2005

Portable remote Raman system for monitoring hydrocarbon, gas hydrates and explosives in the environment.

We report our initial efforts to use a small portable Raman system for stand-off detection and identification of various types of organic chemicals including benzene, toluene, ethyl benzene and xylenes (BTEX). Both fiber-optic (FO) coupled and a directly coupled f/2.2 spectrograph with the telescope have been developed and tested. A frequency-doubled Nd:YAG pulsed laser (20 Hz, 532 nm, 35 mJ/pulse) is used as the excitation source. The operational range of the FO coupled Raman system was tested to 66 m, and the directly coupled system was tested to a distance of 120 m. We have also measured remote Raman spectra of compressed methane gas and methane gas hydrate. The usefulness of the remote Raman system for identifying unknown compounds is demonstrated by measuring stand-off spectra of two plastic explosives, e.g. tri-amino tri-nitrobenzene (TATB) and beta-HMX at 10 m stand-off distance. The remote Raman system will be useful for terrestrial applications such as monitoring environmental pollution, in identifying unknown materials in public places in 10s or less, and for detecting hydrocarbon plumes and gas hydrates on planetary surfaces such as Mars.

Azocines↗

PubMed2005

Micro-Raman studies of hydrous ferrous sulfates and jarosites.

Ferrous sulfates of various hydration states (FeSO(4) X xH(2)O; x=7, 4, 1) and jarosites (MFe(3)(SO(4))(2)(OH)(6); M=Na or K) were synthesized and studied by micro-Raman spectroscopy between 295 and 8K. Spectral analyses of the sulfate and water/hydroxyl vibrational modes are presented. Fingerprint regions attributed to the symmetric (nu(1)) and antisymmetric (nu(3)) stretching vibrations of the sulfate group are found to vary with the degree of hydration in hydrous ferrous sulfate. In jarosites, the Raman shift of the OH stretching mode is related to the type of alkali metal present between the tetrahedral and octahedral layers. The Raman technique can thus unambiguously identify ferrous sulfate of various hydration states and jarosites bearing different alkali metal ions.

Ferric Compounds↗

PubMed2005

X-ray diffraction and Raman studies of the CuGeO3(III)-(IV) transformation under high pressures.

Both X-ray diffraction and Raman spectroscopy measurement were carried out on the same powder sample of CuGeO(3)(III) in a diamond anvil cell to high pressures at room temperature. The phase transformation of (III)-(IV) phase was observed at about 7GPa with both methods and the results were also in accord with previous powder diffraction and Raman measurements, respectively. However, the powder diffraction data were strikingly different from those reported in a recent single-crystal study on the phase (III). It is, therefore, evident that the phase transformations in CuGeO(3)(III) would be as complicated as those in CuGeO(3)(I) and that the monoclinic phase obtained from single-crystal phase (III) at approximately 7GPa is not the phase (IV) previously observed but rather a new phase (IVa) in CuGeO(3).

Minerals↗

PubMed2005

Pulsed remote Raman system for daytime measurements of mineral spectra.

A remote Raman system has been developed utilizing a 532nm pulsed laser and gated intensified charged couple device (ICCD) detector in the oblique geometry. When the system is set for 50m sample distance it is capable of measuring Raman spectra of minerals located at distances in the range of 10-65m from the telescope. Both daytime and nighttime operations are feasible and the spectra of minerals can be measured in a short period of time, of the order of a few seconds. In oblique geometry, measured sampling depth is more than 30m, during which the system maintains very high performance without any adjustments. Much longer sampling depth (0.1-120m) has been observed when the system is configured in the coaxial geometry. Clear advantages of using a gated detection mode over the continuous (CW) mode of operation in reducing the background signal and eliminating long-lived fluorescence signals from the Raman spectra are presented. The performance of the pulsed Raman system is demonstrated by measuring spectra of Raman standards including benzene (C(6)H(6)) and naphthalene (C(10)H(8)), a low Raman cross section silicate mineral muscovite (KAl(2)(Si(3)Al)O(10)(OH)(2)), and a medium Raman cross section mineral calcite (CaCO(3)).

Benzene↗

PubMed2005

Stand-off Raman detection using dispersive and tunable filter based systems.

Small, transportable Raman systems are being developed for stand-off Raman measurements at intermediate ranges (e.g. <20 m) for planetary measurements. Four variations of stand-off Raman systems are described that use a small telescope for light collection that is either fiber-optic or lens-coupled to a detection system. The performance of an acousto-optic tunable filter for wavelength selection and spectral imaging is tested by comparing signal-to-noise ratio and throughput to similar measurements using a conventional spectrograph, and by measuring a variety of organic and inorganic mineral samples at distances up to 15 m. We also determine optimal ICCD gate widths for acquiring remote Raman spectra under high ambient light conditions.

Filtration↗

PubMed2005

Joint analyses by laser-induced breakdown spectroscopy (LIBS) and Raman spectroscopy at stand-off distances.

Raman spectroscopy and laser-induced breakdown spectroscopy (LIBS) of solid samples have both been shown to be feasible with sample-to-instrument distances of many meters. The two techniques are very useful together, as the combination of elemental compositions from LIBS and molecular vibrational information from Raman spectroscopy strongly complement each other. Remote LIBS and Raman spectroscopy spectra were taken together on a number of mineral samples including sulfates, carbonates and silicates at a distance of 8.3 m. The complementary nature of these spectra is highlighted and discussed. A factor of approximately 20 difference in intensity was observed between the brightest Raman line of calcite, at optimal laser power, and the brighter Ca I LIBS emission line measured with 55 mJ/pulse laser power. LIBS and Raman spectroscopy have several obstacles to devising a single instrument capable of both techniques. These include the differing spectral ranges and required detection sensitivity. The current state of technology in these areas is discussed.

Barium Sulfate↗

PubMed2005

Remote Raman and fluorescence studies of mineral samples.

In the present study, we investigated remote laser-induced fluorescence (LIF), at a distance of 4.8 m, of a variety of natural minerals and rocks, and Hawaiian Ti (Cordyline terminalis) plant leaves. These minerals included calcite cleavage, calcite onex and calcite travertine, gypsum, fluorapatite, Dover flint and chalk, chalcedony and nephelene syenite, and rubies containing rock. Pulsed laser excitation of the samples at 355 and 266 nm often resulted in strong fluorescence. The LIF bands in the violet-blue region at approximately 413 and approximately 437 nm were observed only in the spectrum of calcite cleavage. The green LIF bands with band maxima in the narrow range of approximately 501-504 nm were observed in the spectra of all the minerals with the exception of the nephelene syenite and ruby rocks. The LIF red bands were observed in the range approximately 685-711 nm in all samples. Excitation with 532 nm wavelength laser gave broad but relatively low fluorescence background in the low-frequency region of the Raman spectra of these minerals. One microsecond signal gating was effective in removing nearly all background fluorescence (with peak at approximately 610 nm) from calcite cleavage Raman spectra, indicating that the fluorescence was probably from long-lifetime inorganic phosphorescence.

Carbonates↗

PubMed2004

A bivalent ligand (KDN-21) reveals spinal delta and kappa opioid receptors are organized as heterodimers that give rise to delta(1) and kappa(2) phenotypes. Selective targeting of delta-kappa heterodimers.

In view of recent pharmacological studies suggesting the existence of delta-kappa opioid receptor heterodimers/oligomers in the spinal cord, we have synthesized and evaluated (intrathecally in mice) a series of bivalent ligands (KDN series) containing kappa and delta antagonist pharmacophores. Pharmacological and binding data have provided evidence for the bridging of spinal delta-kappa receptor heterodimers by KDN-21 and for their identification as delta(1) and kappa(2). The selectivity profile of KDN-21 and the apparent absence of coupled delta(1)-kappa(2) phenotypes in the brain suggest a new approach for targeting receptors.

Animals↗

PubMed2004

Intermediate-term memory for site-specific sensitization in aplysia is maintained by persistent activation of protein kinase C.

Recent studies of long-term synaptic plasticity and long-term memory have demonstrated that the same functional endpoint, such as long-term potentiation, can be induced through distinct signaling pathways engaged by different patterns of stimulation. A critical question raised by these studies is whether different induction pathways either converge onto a common molecular mechanism or engage different molecular cascades for the maintenance of long-term plasticity. We directly examined this issue in the context of memory for sensitization in the marine mollusk Aplysia. In this system, training with a single tail shock normally induces short-term memory (<30 min) for sensitization of tail-elicited siphon withdrawal, whereas repeated spaced shocks induce both intermediate-term memory (ITM) (>90 min) and long-term memory (>24 hr). We now show that a single tail shock can also induce ITM that is expressed selectively at the trained site (site-specific ITM). Although phenotypically similar to the form of ITM induced by repeated trials, the mechanisms by which site-specific ITM is induced and maintained are distinct. Unlike repeated-trial ITM, site-specific ITM requires neither protein synthesis nor PKA activity for induction or maintenance. Rather, the induction of site-specific ITM requires calpain-dependent proteolysis of activated PKC, yielding a persistently active PKC catalytic fragment (PKM) that also serves to maintain the memory in the intermediateterm temporal domain. Thus, two unique forms of ITM that have different induction requirements also use distinct molecular mechanisms for their maintenance.

Animals↗

PubMed2004

Labor analgesia and cesarean delivery: an individual patient meta-analysis of nulliparous women.

BACKGROUND: The authors performed an individual patient meta-analysis of 2,703 nulliparous women who were randomized to either epidural analgesia or intravenous opioids for pain relief during labor from five trials conducted at their hospital. The primary purpose in this meta-analysis was to evaluate the effects of epidural analgesia during labor on the rate of cesarean delivery. METHODS: Between November 1, 1993, and November 3, 2000, 2,703 nulliparous women (2,188 healthy parturients and 515 women with pregnancy-induced hypertension) in spontaneous labor at term were randomized to receive either epidural analgesia or intravenous opioid analgesia in the five studies. Epidural analgesia was initiated with either epidural bupivacaine or intrathecal sufentanil and was maintained with a low-dose (0.0625% or 0.125%) mixture of bupivacaine with fentanyl. Intravenous opioid analgesia was initiated with 50 mg meperidine and 25 mg promethazine hydrochloride and was maintained with intravenous boluses of meperidine as needed. RESULTS: A total of 1,339 nulliparous women were randomized to receive epidural analgesia, and 1,364 women were randomized to receive intravenous meperidine analgesia. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 10.5% [140 of 1,339] vs. intravenous meperidine analgesia, 10.3% [141 of 1,364]; adjusted odds ratio, 1.04; 95% confidence interval, 0.81-1.34; P = 0.920). Significantly more women randomized to epidural analgesia had forceps deliveries compared to meperidine analgesia (13% [172 of 1,339] vs. 7% [101 of 1,364]; adjusted odds ratio, 1.86; 95% confidence interval, 1.43-2.40; P < 0.001). Epidural women had longer first and second stages of labor. Women who received epidural analgesia reported lower pain scores during labor and delivery compared to women who received intravenous meperidine analgesia. CONCLUSION: Epidural analgesia compared to intravenous meperidine analgesia during labor does not increase the number of cesarean deliveries.

Adult↗

PubMed2003

Differential role of mitogen-activated protein kinase in three distinct phases of memory for sensitization in Aplysia.

The mitogen-activated protein kinase (MAPK) pathway has been implicated recently in synaptic plasticity and memory. Here we used tail shock-induced sensitization of the tail-elicited siphon withdrawal reflex in Aplysia to examine the role of MAPK in three different phases of memory. We show that a specific pattern of serotonin (5-HT) application that produces intermediate-term and long-term synaptic facilitation (ITF and LTF, respectively) of the sensory-motor (SN-MN) synapses in Aplysia leads to sustained activation of extracellular signal-regulated kinase in the ventrocaudal cluster sensory neurons (SNs), which include the tail SNs. Furthermore, repeated tail shocks that induce intermediate-term and long-term memory (ITM and LTM, respectively) for sensitization also lead to sustained MAPK activation in the SNs. Given these results, we next examined the requirement of MAPK activity in (1) SN-MN synaptic facilitation and (2) memory for sensitization in Aplysia, by inhibiting MEK, the upstream kinase that phosphorylates and activates MAPK. In cellular experiments, we show that MAPK activity is required for ITF of tail SN-tail MN synapses, and, in parallel behavioral experiments, we show that ITM requires MAPK activity for its induction but not its expression. In contrast, short-term memory for sensitization does not require MAPK activity. Finally, 5-HT-induced LTF has been shown previously to require MAPK activity. Here we show that LTM for sensitization also requires MAPK activity. These results provide evidence that MAPK plays important roles specifically in long-lasting phases of synaptic plasticity and memory.

Action Potentials↗

PubMed2003

Inhibition of calcineurin facilitates the induction of memory for sensitization in Aplysia: requirement of mitogen-activated protein kinase.

The induction of both synaptic plasticity and memory is thought to depend on the balance between opposing molecular regulatory factors, such as protein kinases and phosphatases. Here we show that inhibition of protein phosphatase 2B (calcineurin, CaN) facilitates the induction of intermediate-term memory (ITM) and long-term memory (LTM) for tail shock-induced sensitization in Aplysia without any effect on short-term memory. To identify the molecular cascade underlying the improvement of memory by inhibition of CaN, we examined the role of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase (MAPK). Molecular experiments revealed that one pulse of serotonin, which by itself does not activate MAPK, leads to significant MAPK activation in the sensory neurons of the pleural ganglia when CaN is inhibited. Extending these observations, behavioral experiments showed that the facilitated induction of ITM and LTM produced by CaN inhibition depends on MAPK activity. These results demonstrate: (i) that CaN acts as an inhibitory constraint in the formation of long-lasting phases of memory, and (ii) that facilitated induction of ITM and LTM by CaN inhibition requires MAPK activity.

Animals↗

PubMed2003

Activation of a tyrosine kinase-MAPK cascade enhances the induction of long-term synaptic facilitation and long-term memory in Aplysia.

Tyrosine kinases have been implicated in cellular processes thought to underlie learning and memory. Here we show that tyrosine kinases play a direct role in long-term synaptic facilitation (LTF) and long-term memory (LTM) for sensitization in Aplysia. Tyrosine kinase activity is required for serotonin-induced LTF of sensorimotor (SN-MN) synapses, and enhancement of endogenous tyrosine kinase activity facilitates the induction of LTF. These effects are mediated, at least in part, through mitogen-activated protein kinase (MAPK) activation and are blocked by transcriptional and translational inhibitors. Moreover, brain-derived neurotrophic factor (BDNF) also enhances the induction of LTF in a MAPK-dependent fashion. Finally, activation of endogenous tyrosine kinases enhances the induction of long-term memory for sensitization, and this enhancement also requires MAPK activation. Thus, tyrosine kinases, acting through MAPK, play a pivotal role in LTF and LTM formation.

Animals↗