Biomedical subjects

D Patten

Publications and source records attributed to D Patten.

5 recordsLinked to original sources

PubMed1999

Electroglottographic tracking of phonatory response to Botox.

Botox injection into the thyroarytenoid muscle is thought to alter the glottal competence and laryngeal adduction of patients with adductor spasmodic dysphonia (ADSD). Hypofunctional responses to treatment have been rated subjectively and inferred from postinjection breathy voice, aphonia, midline glottal gap, or subclinical aspiration. Clinical experience suggests that temporary hypofunction varies in duration and severity among patients. This study used electroglottographic measures to examine changes over time in glottal competence during the relatively stable phonation produced by 5 patients with ADSD. Hierarchical linear modeling was used to test 3 hypotheses: (a) that reduced laryngeal adduction would occur during the first 3 weeks postinjection, followed by a reversal; (b) that patients' hypofunctional response curves would differ one from another; and (c) that changes in adduction, if present, would be related to changes in severity ratings of ADSD symptoms. For 3 participants, significant hypoadduction occurred after injection and reversed toward preinjection level over an 8-week period. Two participants demonstrated a flat or increasing vocal fold contact response curve during the early postinjection period. Observations were consistent with the previously reported differences and possibly complex relation between the resolution of breathy hypofunction and ultimate return of ADSD symptoms.

Adult↗

PubMed1999

Subunit-selective modulation of GABAA receptors by the non-steroidal anti-inflammatory agent, mefenamic acid.

Mefenamic acid (MFA) has anti-convulsant and pro-convulsant effects in vivo, and has been shown to potentiate and inhibit GABAA (gamma-aminobutyric acid) receptors in vitro. In this study, whole-cell currents were recorded from Xenopus oocytes and human embryonic kidney (HEK) cells expressing human recombinant GABAA receptors to resolve the molecular mechanisms by which MFA modulates GABAA receptor function. We demonstrate that MFA potentiated GABA-activated currents for alpha1beta2 gamma2S (EC50 = 3.2 +/- 0.5 microM), but not for alpha1beta1 gamma2S receptors. MFA also enhanced GABA-activated responses and directly activated alpha1beta2/beta3 GABAA receptors, but inhibited responses to GABA on alpha1beta1 constructs (IC50 = 40 +/- 7.2 microM). A comparison of beta1, beta2 and beta3 subunits suggested that the positive modulatory action of MFA involved asparagine (N) 290 in the second transmembrane domain (TM2) of the beta2 and beta3 subunits. Mutation of N290 to serine (S) markedly reduced modulation by MFA in alpha1beta2(N290S)gamma2S receptors, whereas alpha1beta1(S290N)gamma2S constructs revealed potentiated responses to GABA (EC50 = 7.8 +/- 1.7 microM) and direct activation by MFA. The potentiation by MFA displayed voltage sensitivity. The direct activation, potentiation and inhibitory aspects of MFA action were predominantly conferred by the beta subunits as the spontaneously active homomeric beta1 and beta3 receptors were susceptible to modulation by MFA. Molecular comparisons of MFA, loreclezole and etomidate, agents which exhibit similar selectivity for GABAA receptors, revealed their ability to adopt similar structural conformations. This study indicates that N290 in TM2 of beta2 and beta3 subunits is important for the regulation of GABAA receptor function by MFA. Our data provide a potential molecular mechanism for the complex central effects of MFA in vivo.

Amino Acid Sequence↗

PubMed1983

Scrotal ultrasonography.

Scrotal ultrasonography was performed on 43 patients with a diagnostic accuracy rate of 88 per cent. With a small parts 7.5 MHz. real-time ultrasound scanner a clear distinction between gonadal and epididymal pathologic conditions can be achieved in the majority of cases.

Genital Diseases, Male↗

PubMedDate not supplied

Purification and amino acid sequence of a highly insecticidal toxin from the venom of the brazilian spider Phoneutria nigriventer which inhibits NMDA-evoked currents in rat hippocampal neurones.

A new insecticidal toxin Tx4(5-5) was isolated from the fraction PhTx4 of the venom of the spider Phoneutria nigriventer by reverse phase high performance liquid chromatography (HPLC) and anion exchange HPLC. The complete amino acid sequence determined by automated Edman degradation showed that Tx4(5-5) is a single chain polypeptide composed of 47 amino acid residues, including 10 cysteines, with a calculated molecular mass of 5175 Da. Tx4(5-5) shows 64% of sequence identity with Tx4(6-1), another insecticidal toxin from the same venom. Tx4(5-5) was highly toxic to house fly (Musca domestica), cockroach (Periplaneta americana) and cricket (Acheta domesticus ), producing neurotoxic effects (knock-down, trembling with uncoordinated movements) at doses as low as 50 ng/g (house fly), 250 ng/g (cockroach) and 150 ng/g (cricket). In contrast, intracerebroventricular injections (30 microg) into mice induced no behavioural effects. Preliminary electrophysiological studies carried out on whole-cell voltage-clamped rat hippocampal neurones indicated that Tx4(5-5) (at 1 microM) reversibly inhibited the N-methyl-D-aspartate-subtype of ionotropic glutamate receptor, while having little or no effect on kainate-, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid- or gamma-aminobutyric acid-activated currents.

Amino Acid Sequence↗

PubMedDate not supplied

An electrophysiological study of the effects of propofol on native neuronal ligand-gated ion channels.

1. Pharmacological evidence suggests that some of the clinical actions of propofol may be mediated, at least in part, by positive modulation of the GABA(A) receptor chloride channel. The effect of propofol at other native neuronal ligand-gated ion channels is unclear. 2. To gain some insight into the effects of propofol at a range of native neuronal receptors, the present study has used an extracellular recording technique and determined its effects at GABA(A), 5-HT3, P2X and nicotinic acetylcholine (nACh) receptors of the rat isolated vagus nerve and the GABA(A) and strychnine-sensitive glycine receptor of the rat isolated optic nerve. In addition, we have used patch-clamp recording techniques to further investigate the effects of propofol at the GABA(A) and strychnine-sensitive glycine receptors in rat cultured hippocampal neurons. 3. Propofol (0.3-100 micromol/L) concentration-dependently potentiated submaximal GABA-evoked responses in the vagus nerve and shifted the GABA concentration-response curve to the left. In contrast, propofol at concentrations ranging from 1 to 10 micromol/L had little or no effect on 5-HT3, P2X or nACh receptor-mediated responses in the vagus nerve but, at 100 micromol/L, propofol inhibited these responses to approximately 50% of control. In the optic nerve, EC20 GABA-evoked responses were also potentiated by propofol (10 micromol/L), while EC20 glycine-evoked responses were minimally enhanced. 4. Further investigations using cultured hippocampal neurons showed that submaximal (10 micromol/L) GABA-evoked currents were potentiated by propofol (1-10 micromol/L), in a non-voltage-dependent manner, whereas submaximal (100 micromol/L) glycine-evoked currents were unaffected. 5. These data suggest that propofol, at therapeutic concentrations, exerts its principle pharmacological actions at GABA(A) receptors with relatively little effect at other neuronal ligand-gated ion channels.

Anesthetics, Intravenous↗