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R L Martin

Publications and source records attributed to R L Martin.

At least 55 records · Page 3Linked to original sources
PubMed1997

The three-dimensional frequency organization of the inferior colliculus of the cat: a 2-deoxyglucose study.

The 3-dimensional (3-D) functional organization of the cat's inferior colliculus (IC) was examined using the 2-deoxyglucose method. Animals were dichotically stimulated with pure tone stimuli at an intensity of 80 dB SPL. Autoradiographic sections from these animals, cut in the three standard planes, were serially reconstructed to reveal the 3-D topography of the isofrequency sheets of labelling. In all 3-D reconstructions, the isofrequency sheets extend rostrocaudally through the IC with the rostral aspect of the sheet being situated more ventral than its caudal aspect. In the mediolateral dimensions, sheets are angled at between 40 degrees and 60 degrees to the horizontal, running from a dorsomedial to a ventrolateral position. The low-frequency sheets (0.5 and 2 kHz) are dorsolaterally convex and situated in the dorsolateral region of the IC. The 4 and 10 kHz isofrequency sheets have a helical structure and are situated in the mid-region of the IC. The high-frequency sheets (20 and 30 kHz) are dorsolaterally concaved and situated in the ventromedial region of the IC. The topography of these isofrequency sheets generally agree with, and extended our knowledge of, the tonotopic organization of the IC as derived from electrophysiological studies. The functional organization revealed by the 2-deoxyglucose method only partially correlated with the neural laminae in the anatomical models of the IC proposed by Rockel and Jones [J. Comp. Neurol. 147 (1973) 11-60] and Oliver and Morest [J. Comp. Neurol. 222 (1984) 237-264]. It is therefore concluded that the neural laminar organization of the IC may not be a necessary substrate for the tonotopic organization seen the IC.

Acoustic Stimulation↗
PubMed1997

Intensity and frequency functions of [14C]2-deoxyglucose labelling in the central nucleus of the inferior colliculus in the cat.

The frequency organization of the central nucleus of the inferior colliculus (ICC) in the anesthetised cat was quantitatively mapped using [14C]2-deoxyglucose. From a standardised rostrocaudal region of the ICC, the position of peak selective labelling along the tonotopic axis closely conformed to the reported tonotopic organization of this nucleus. The position of the peak was found not to significantly change its position along the tonotopic axis with increasing stimulus intensity. However, the amplitude of peak uptake and width of selective labelling were shown to monotonically increase with increase in stimulus intensity. The increase in width of selective labelling, about the position of peak uptake, showed a slight asymmetry toward the high-frequency regions of the ICC. A 2-DG frequency-position function for the ICC, similar to that for the cochlea, enabled the width of 2-DG bands to be expressed in terms of their frequency spread along the tonotopic axis. This inturn enabled 2-DG tuning curves to be plotted which, when compared to electrophysiologically determined tuning curves, showed marked similarities. The minimum threshold and width (Q10) of these 2-DG tuning curves fell within the range reported for single units in the cat auditory pathway.

Acoustic Stimulation↗
PubMed1997

Extracellular calcium stimulates Na(+)-dependent putrescine uptake in B16 melanoma cells.

The regulation of putrescine transport in difluoromethylornithine-treated B16 melanoma cells by extracellular Ca2+ has been investigated. It was found that physiological concentrations of Ca2+ were essential for optimum uptake of putrescine and spermidine, Mg2+, albeit at higher concentrations, also could potentiate polyamine transport. The maximum rate of putrescine uptake increased from 1698 +/- 67 pmol/min/min/mg DNA in the absence of Ca2+ to 3100 +/0 98 pmol/min/mg DNA in the presence of 0.5 mM Ca2+. There was no change in Km. While Ca2+ enhanced transport of both putrescine and spermidine it did not affect the uptake of deoxyglucose, thymidine or leucine. Putrescine did not alter Ca2+ fluxes suggesting that the two cations do not share a common transport system. The effects of Ca2+ on putrescine uptake appeared to be mediated extracellularly firstly because Ca2+ did not potentiate putrescine uptake in the presence of A23187 and secondly, because the effects of Ca2+ were completely inhibited by the lanthanide Tb3+, which binds to calcium-dependent proteins and does not readily cross biological membranes, Ca2+ did not affect putrescine transport in the absence of extracellular Na+. Moreover, the rate of putrescine uptake in the absence of Ca2+ was similar to that in the absence of extracellular Na+. The results from this study indicate that polyamine transport is stimulated by extracellular Ca2+ and suggest that Ca2+ is required for activity of the Na(+)-dependent transporter only. This transporter appears to possess a regulatory binding site for divalent cations.

Animals↗
PubMed1997

Alterations in ATP-sensitive potassium channel sensitivity to ATP in failing human hearts.

Little is known about the involvement of preexisting heart disease on characteristics of ATP-sensitive K+ channels [I[K(ATP)]] in human heart. We have characterized I[K(ATP)] in isolated cardiac myocytes from patients with congestive heart failure (HF) and compared these channel characteristics with those from donor hearts (healthy control) using the patch-clamp technique. During metabolic inhibition induced by treatment with cyanide (1 mM) and 2-deoxyglucose (10 mM), action potential shortening occurred in atrial myocytes isolated from both HF and donors, but this response was significantly greater and sooner in HF than in donors. The action potential duration at 90% repolarization was 24.7 +/- 4.1% (n = 15) of control in HF, whereas it was 58.7 +/- 5.9% (n = 10, P < 0.001) of control in donors measured at 30-min metabolic inhibition. The shortening of the action potential was partially reversed by glibenclamide (0.5 microM) in both groups. Consistent with the action potential measurements, the whole cell membrane current response to metabolic inhibition, evaluated by the differential current measurement, was sooner and greater in HF than in donors. Single-channel atrial I[K(ATP)] from both HF and donors, recorded in the excised inside-out patch configuration, exhibited bursting opening, conductance, and gating behaviors that did not differ between the two groups. However, the concentration of ATP at half-maximal inhibition of the channel in HF was greater (131.0 microM) than in donors (26.1 microM). We conclude that I[K(ATP)] in cardiac myocytes from patients with HF has channel characteristics substantially similar to those in donors, but that the channel is less sensitive to ATP inhibition in HF than in donors.

Action Potentials↗
PubMed1997

Response properties of neurons in the inferior colliculus of the monaurally deafened ferret to acoustic stimulation of the intact ear.

Response properties of neurons in the central nucleus of the inferior colliculus (ICC) were investigated after unilateral cochlear removal at various ages during infancy. Nineteen ferrets had the right cochlea surgically ablated, either in adulthood or on postnatal day (P) 5, 25, or 40, 3-18 mo before recording. Adult ablations were made on the same day as ("acute," n = 3), or 2-3 mo before ("chronic," n = 3), recording. Two ferrets were left binaurally intact. Single-unit (n = 702) and multiunit (n = 1,819) recordings were made in the ICC of barbiturate-anesthetized ferrets ipsilateral (all ages) or contralateral (P5 and acute adult only) to the intact ear. In binaurally intact animals, tonal stimulation of the contralateral ear evoked excitatory activity at the majority (94%) of recording loci, whereas stimulation of the ipsilateral ear evoked activity at only 33% of recording loci. In acutely ablated animals, the majority of contralateral (90%) and ipsilateral (70%) loci were excited by tonal stimulation of the intact ear. In chronically ablated animals, 80-90% of loci were excited by ipsilateral stimulation. Single-unit thresholds were generally higher for low-best frequency (BF) than for high-BF units, and higher in the ipsilateral than in the contralateral ICC. Analysis of covariance showed highly significant differences between all of the ipsilateral and contralateral groups, but no effects of age at ablation or survival time following ablation, other than that the group ablated at P25 had higher mean ipsilateral thresholds than the groups ablated at P5 or, acutely, in adulthood. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in dynamic ranges of ipsilateral ICC unit rate-intensity functions relative to acutely ablated animals. Dynamic ranges of units in the contralateral ICC of P5-ablated ferrets were also significantly increased compared with those of acutely ablated animals. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in single-unit spontaneous discharge rates in the ICC ipsilateral but not contralateral (P5 only) to the intact ear. These data show that unilateral cochlear removal in adult ferrets leads to a rapid and dramatic increase in the proportion of neurons in the ICC ipsilateral to the intact ear that is excited by acoustic stimulation of that ear. In addition, the data confirm that, in ferrets, cochlear removal in infancy leads to a further increase in responsiveness of individual neurons in the ipsilateral ICC. Finally, the data show that responses in the ICC contralateral to the intact ear are largely but not completely unchanged by unilateral cochlear removal.

Acoustic Stimulation↗
PubMed1996

Sex ratios in fetuses and liveborn infants with autosomal aneuploidy.

Ten data sources were used substantially to increase the available data for estimating fetal and livebirth sex ratios for Patau (trisomy 13), Edwards (trisomy 18), and Down (trisomy 21) syndromes and controls. The fetal sex ratio estimate was 0.88 (N = 584) for trisomy 13, 0.90 (N = 1702) for trisomy 18, and 1.16 (N = 3154) for trisomy 21. All were significantly different from prenatal controls (1.07). The estimated ratios in prenatal controls were 1.28 (N = 1409) for CVSs and 1.06 (N = 49427) for amniocenteses, indicating a clear differential selection against males, mostly during the first half of fetal development. By contrast, there were no sex ratio differences for any of the trisomies when comparing gestational ages < 16 and > 16 weeks. The livebirth sex ratio estimate was 0.90 (N = 293) for trisomy 13, 0.63 (N = 497) for trisomy 18, and 1.15 (N = 6424) for trisomy 21, the latter two being statistically different than controls (1.05) (N = 3660707). These ratios for trisomies 13 and 18 were also statistically different than the ratio for trisomy 21. Only in trisomy 18 did the sex ratios in fetuses and livebirths differ, indicating a prenatal selection against males > 16 weeks. No effects of maternal age or race were found on these estimates for any of the fetal or livebirth trisomies. Sex ratios for translocations and mosaics were also estimated for these aneuploids. Compared to previous estimates, these results are less extreme, most likely because of larger sample sizes and less sample bias. They support the hypothesis that these trisomy sex ratios are skewed at conception, or become so during embryonic development through differential intrauterine selection. The estimate for Down syndrome livebirths is also consistent with the hypothesis that its higher sex ratio is associated with paternal nondisjunction.

Adult↗
PubMed1996

Ionic basis of the membrane potential responses of rat dorsal vagal motoneurones to HEPES buffer.

The effects of 10 mM HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid) buffered artificial cerebrospinal fluid (aCSF) on membrane potential and the action potential were studied in 93 dorsal vagal motoneurones (DVMs) using an in vitro slice preparation of the rat medulla. Changing from bicarbonate/CO2 aCSF to HEPES aCSF resulted in a depolarisation of 6.0 +/- 0.6 mV and an increase in input resistance (RIn; n = 61). In the presence of 5 mM 4-AP, HEPES either had little effect (n = 9) or hyperpolarised the membrane (n = 10). Mn2+ (3 mM) or Ni2+ (200 microM) abolished the hyperpolarisation and its associated increase in RIn. In voltage-clamp studies 5 mM 4-AP eliminated a transient outward current and Ni2+ blocked an inactivating inward current. It is concluded that HEPES buffer reduces the contribution of the A current to resting membrane potential and also reduces a Ni(2+)-sensitive transient ICa.

4-Aminopyridine↗
PubMed1996

Cyclosporin A potentiates estradiol-induced expression of the cathepsin D gene in MCF7 breast cancer cells.

Although the physiological role of the immunophilins cyclophilin-40 and FKBP52 is unknown, their identification as components of the unactivated estrogen receptor has raised the possibility that they might influence receptor activity in response to the binding of immunosuppressants cyclosporin A and FK506, respectively. We have used Northern analysis to determine the influence of cyclosporin A on the expression of the estrogen-inducible cathepsin D gene in human MCF7 breast cancer cells. We report that 1-3 microM cyclosporin A can potentiate cathepsin D mRNA expression by up to 2-fold in cells treated with 10(-12) to 10(-10) M estradiol. A decreased potentiation effect was noted at higher hormone concentrations. Cyclosporin A alone was unable to induce cathepsin D expression and the increased gene activation observed with combined estradiol/cyclosporin A treatment was negated by the antiestrogen ICI 164,384. Our results suggest that the increased potency of estradiol in the presence of cyclosporin A is associated with an enhanced transcriptional activity of the estrogen receptor and support a role for receptor-associated cyclophilin-40 in the activation process.

Breast Neoplasms↗
PubMed1996

Molecular chaperones and the centrosome. A role for TCP-1 in microtubule nucleation.

Molecular chaperones play an important role in facilitating the proper maturation of many newly synthesized proteins. Here we provide evidence that molecular chaperones also participate in regulating the assembly of the microtubule cytoskeleton. Via indirect immunofluorescence analysis, both hsp 73 and TCP-1 localized within the centrosome in interphase and mitotic cells. These proteins, along with the centrosome-specific protein, pericentrin, were also present within an enriched preparation of centrosomes. Because the centrosome serves as an initiation site for microtubule growth, we examined the ability of cells to regrow their microtubule network in the presence of hsp 73 or TCP-1 specific antibodies. Purified tubulin and GTP were added to cells following the depolymerization and extraction of cellular microtubules. Microtubules were observed to nucleate off the centrosome using this system, even in the presence of anti-hsp 73 antibodies. Incubation with anti-TCP-1 antibodies, however, blocked microtubule regrowth off the centrosome. Similarly, anti-TCP-1 antibodies microinjected into living cells first treated with nocodazole also inhibited the regrowth of the microtubule network following removal of the microtubule poison. Our results complement earlier genetic studies in yeast implicating a role for TCP-1 in microtubule mediated processes, and may help to explain the previously reported mitotic and meiotic abnormalities associated with TCP-1 mutations.

Amino Acid Sequence↗
PubMed1996

Cardiac sodium channels expressed in a peripheral neurotumor-derived cell line, RT4-B8.

RT4-B is one of several cell lines derived from a multipotent stem cell line, RT4-AC, which originated from a rat peripheral neurotumor. Based on Northern blot and ribonuclease protection experiments, RT4-B8 cells have been proposed to express rat cardiac Na channel mRNA as the major isoform. We report here direct electrophysiological evidence that the expressed voltage-gated Na channels in the RT4-B8 cell line are of the cardiac phenotype with no evidence for subpopulations expressing other Na channel isoforms. Current activation half point (conductance) was -41 +/- 5 mV (n = 7) and the steady-state voltage-dependent availability half point was -89 +/- 1 mV. As expected for cardiac Na channels, the half concentration of block for tetrodotoxin block was 0.74 microM, for saxitoxin (STX) was 0.15 microM, and for the class 2B divalent cation Cd2+ was 67 microM. Block was well described by single-site dose-response relationships with no indication of a subpopulation with "neuronal" affinity. Single-channel conductance (140 mM Na+) was 10 pS and predicted the average number of channels open at peak Na current to be 3 channels/microns2. [3H]STX binding data were also consistent with a single population of low-affinity STX binding sites and predicted channel density to be 11 sites/microns2. No inwardly or outwardly rectifying K or Ca currents were detected electrophysiologically, although in some cells a small time-independent Cl current was detected. Reverse transcription-polymerase chain reaction of mRNA isolated from RT4-B8 cells demonstrated the presence of rat cardiac (rH1) and brain IIa alpha-subunit mRNA, as well as mRNA for the Na channel beta 1-subunit. Northern blot analysis confirmed the predominance of the rat cardiac Na mRNA compared with brain IIa. The beta 1-subunit mRNA levels were significantly lower than those detected in rat brain and heart mRNA but were comparable to the low level of beta 1-subunit mRNA detected in isolated rat ventricular myocytes.

Animals↗
PubMed1996

Plantar pressure measurements during ambulation in weightbearing conventional short leg casts and total contact casts.

Total contact casts have been shown to be effective in healing plantar neuropathic ulcerations. The proposed mechanism of action is reduction of pressure over the ulcer during ambulation. However, there is little information to support this contention. Plantar pressure distribution was studied using standard short leg casts and total contact casts in normal feet. Both types of casts reduced forefoot pressure in study subjects. This occurred because of an increase in plantar surface area exposed to weightbearing forces. While increased force was shifted to the midfoot, there was no increase in pressure due to a corresponding increase in midfoot surface area exposed to this force. No significant difference was noted between standard short leg casts and total contact casts.

Adult↗
PubMed1996

Plantar pressure analysis of diabetic rockerbottom deformity in total contact casts.

In a previous study, we examined plantar pressures under normally arched individuals in casts. The investigation described in this article was designed to assess plantar pressure distribution in subjects with Charcot midfoot collapse and rockerbottom deformity in standard short leg casts and total contact casts. Our results show that both types of casts significantly reduced midfoot pressures. No significant differences were noted between the two casting groups.

Aged↗
PubMed1995

Obsessive-compulsive disorder, trichotillomania, and anorexia nervosa: a case report.

We report a case study of an 18-year-old female who presented with symptoms associated with several discrete diagnostic syndromes: obsessive-compulsive disorder, trichotillomania, major depression, and anorexia nervosa. Improvement in each occurred after treatment with the serotonin selective reuptake inhibitor, fluoxetine, suggesting that such syndromes share a common serotonin neurotransmitter disturbance. Furthermore, the combined effects of medication and psychotherapy resulted in improvement in assertiveness, sense of security, self-worth, flexibility, and self-regulation. We discuss the pharmacological and psychotherapeutic implications of possible psychophysiologic similarities among the previously mentioned syndromes.

Adolescent↗
PubMed1995

A pharmacological and biochemical investigation of the venom from the platypus (Ornithorhynchus anatinus).

In this study several activities of the venom of Ornithorhynchus anatinus have been investigated. Whole venom induced local oedema after subplantar injection and produced relaxation of the rat uterus in vitro. The relaxant activity was partially purified by gel permeation HPLC and subsequent analyses by SDS-PAGE revealed that this activity was associated with a 4200 mol. wt peptide. The N-terminal partial sequence of this peptide exhibited substantial identity with human and porcine C-type natriuretic peptide (CNP). Three other major proteins isolated from the venom had mol. wts of 140,000, 55,000 and 16,000. None was found to have any sequence homology with proteins listed in the SwissProt database. The 140,000 mol. wt protein exhibited hyaluronidase activity but the nature of the 55,000 and 16,000 mol. wt proteins remains to be determined. Platypus venom also exhibits protease activity, although the concentration of proteolytic enzymes was too low to be visualised by SDS-PAGE using Coomassie staining.

Amino Acid Sequence↗
PubMed1995

Onset of ototoxicity in the cat is related to onset of auditory function.

Cats are altricial mammals; they are born deaf and undergo rapid maturation of the auditory periphery late in the first and throughout the 2nd week of life. Previous studies, using multiple aminoglycoside administration over several days or weeks, have indicated that there is a reduction in the degree of ototoxicity in young animals provided the drug is administered prior to the onset of auditory function. In order to provide a more precise relationship between the degree of ototoxicity and auditory development, we used a single administration of Kanamycin (KA) and the loop diuretic ethacrynic acid (EA), as the co-administration of these drugs is known to produce a rapid and profound hearing loss in adult animals. Thirty kittens were administered with KA and EA at ages that varied from 2 to 16 days after birth (DAB) using a fixed dose per kilogram body weight sufficient to profoundly deafen adult animals. All animals made an uneventful recovery from the procedure. At 26 DAB, tone-pip-evoked auditory brainstem responses (ABR) were recorded from each animal in order to establish the extent of the hearing loss. The degree of hearing loss was compared with normal ABR audiograms recorded from 6 age-matched control animals. All animals treated with KA/EA at 9 DAB or older had a profound hearing loss similar to adult animals. Animals treated between 2 and 8 DAB exhibited severe high-frequency hearing losses. The extent of the loss was correlated with age (r = 0.63) and body weight (r = 0.72) such that hearing loss tended to spread towards lower frequencies as age and/or weight increased. All animals exhibited bilaterally symmetrical hearing losses which remained relatively stable over monitoring periods of up to 6 months following the drug treatment. These findings imply that the onset of ototoxicity is related, at least in part, to the onset of auditory function in the kitten. The rapid onset of deafness following this procedure makes it a useful technique in the study of both ototoxicity and cochlear development.

Aging↗
PubMed1995

Comparison of the effects of internal [Mg2+] on IK1 in cat and guinea-pig cardiac ventricular myocytes.

The effects of internal Mg2+ (Mg2+i) on processes underlying the inward rectification of the cardiac IK1 in enzymatically isolated cardiac ventricular myocytes (CVM) obtained from cat, guinea pig and rabbit were compared using the whole-cell and excised inside-out patch configurations of the voltage-clamp technique. In confirmation of the findings of other investigators, Mg(2+)i-sensitive outward IK1 currents could be elicited from guinea pig CVM at 15 degrees C when Mg2+i was reduced from 1 mM to less than 1 microM, suggesting that Mg2+i has an important role in the inward rectification of IK1 in guinea pig CVM at unphysiologically low temperatures. However, as temperature was raised to more physiological levels (e.g., 30 degrees C), Mg(2+)i-sensitive outward IK1 currents could no longer be evoked. In contrast with the results obtained with guinea pig CVM, IK1 remained inwardly rectifying in cat and rabbit CVM independent of the Mg2+i concentration ([Mg2+]i) at 37 degrees, 15 degrees, 10 degrees, and 5 degrees C. Reduced [Mg2+]i at low temperature (15 degrees C), shifted the voltage dependence of guinea pig IK1 activation in the depolarizing direction; this resulted in an apparent linearization of IK1 conductance. When the range of the membrane potential examined was expanded to include voltages up to +80 mV, the guinea pig IK1 was found to exhibit inward rectification with the inflection in the I-V relationship that is found at approximately EK at normal temperature, also shifted 80 mV or more to much less negative voltages at low temperatures. In contrast, irrespective of [Mg2+]i or temperature, the voltage dependencies of the IK1 activation curves for both cat and rabbit myocytes were not changed from that defined when [Mg2+]i was 1 mM and temperature was 37 degrees C. We propose that Mg2+i affects inward rectification of IK1 in cold guinea pig CVM by altering the voltage dependence of activation.

Animals↗
PubMed1995

Simultaneous measurement of pH and membrane potential in rat dorsal vagal motoneurons during normoxia and hypoxia: a comparison in bicarbonate and HEPES buffers.

1. The effects of oxygenated and hypoxic bicarbonate/CO2, 10 and 25 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered artificial cerebrospinal fluid (ACSF) have been studied in a rat brain slice preparation. Double-barreled pH-selective microelectrodes were used to measure intracellular pH (pHi) and membrane potential in dorsal vagal motoneurons (DVMs) and to measure extracellular pH (pHe) in the dorsal vagal motonucleus. 2. In bicarbonate ACSF, pHi averaged 7.24 +/- 0.05 (mean +/- SE, n = 21) and ranged from 6.86 to 7.79 pH units. pHe averaged 7.13 +/- 0.08 (n = 10). 3. On changing from oxygenated bicarbonate ACSF to either 10 or 25 mM HEPES ACSF, pHi decreased by 0.13-0.15 units, and the membrane depolarized by 10-11 mV. pHe also decreased in 10 mM HEPES ACSF (pHe 6.89 +/- 0.02, n = 8) but not in 25 mM HEPES ACSF (pHe 7.15 +/- 0.06, n = 3). In most neurons changes in pHi preceded changes in membrane potential. 4. In bicarbonate ACSF and in 25 mM HEPES ACSF, there was a significant linear relationship between prehypoxic pHi and the direction and amplitude of the hypoxia-induced membrane potential change (either an hyperpolarization or a depolarization). 5. In 10 mM HEPES ACSF, hypoxia always induced a depolarization; there was no correlation between prehypoxic pHi and the membrane potential response. 6. In bicarbonate ACSF and in 10 and 25 mM HEPES ACSF, hypoxia resulted in intracellular and extracellular acidification. However, the extracellular acidification in hypoxic 10 mM HEPES buffer was most pronounced (pH 6.40 +/- 0.11, n = 8), reflecting a preexisting extracellular acidification in oxygenated 10 mM HEPES buffer. 7. Various hypotheses that could give rise to a relationship between changes in membrane potential and pH are discussed; arguments are presented in favor of the concept that modulation of ion channels by either pHi or pHe, or both, is responsible for the observed correlations.

Animals↗