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R L Martin

Publications and source records attributed to R L Martin.

At least 19 recordsLinked to original sources
PubMed1997

Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase.

Macrophage elastase (ME) was originally named when metal-dependent elastolytic activity was detected in conditioned media of murine macrophages. Subsequent cDNA cloning of the mouse and human enzyme demonstrated that ME is a distinct member of the matrix metalloproteinase family. To date, the catalytic parameters that describe the hydrolysis of elastin by ME have not been quantified and its activity against other matrix proteins have not been described. In this report, we have examined the action of purified recombinant human ME (rHME), produced in Escherichia coli, on elastin and other extracellular matrix proteins. On a molar basis, rHME is approximately 30% as active as human leukocyte elastase in solubilizing elastin. rHME also efficiently degrades alpha1-antitrypsin (alpha1-AT), the primary physiological inhibitor of human leukocyte elastase. In addition, rHME efficiently degrades fibronectin, laminin, entactin, type IV collagen, chondroitan sulfate, and heparan sulfate. These results suggest that HME may be required for macrophages to penetrate basement membranes and remodel injured tissue during inflammation. Moreover, abnormal expression of HME may contribute to destructive processes such as pulmonary emphysema and vascular aneurysm formation. To further understand the specificity of HME, the initial cleavage sites in alpha1-AT have been determined. In addition, the hydrolysis of a series of synthetic peptides with different P'1 residues has been determined. rHME can accept large and small amino acids at the P'1 site, but has a preference for leucine.

Amino Acid Sequence↗
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↗
PubMed1995

DSM-IV field trial: testing a new proposal for somatization disorder.

OBJECTIVE: The purpose of this study was to evaluate for APA a proposed strategy to diagnose somatization disorder for possible inclusion in DSM-IV. METHOD: Five sites--Washington University, University of Kansas, University of Iowa, University of Arkansas, and Mount Sinai Medical Center in New York--participated in a collaborative field trial. Female subjects (N = 353) were recruited from several different services (psychiatry, internal medicine, and family practice) and were evaluated for the presence or absence of the disorder. This assessment was performed with a new instrument constructed by combining all the criteria for somatization disorder from the proposed criteria for DSM-IV, DSM-III, DSM-III-R, Perley-Guze, and proposed criteria for ICD-10. RESULTS: A high level of concordance was found between the proposed diagnostic strategy for DSM-IV and the current criteria (DSM-III-R), as well as the earlier criteria (Perley-Guze and DSM-III). The ICD-10 criteria agreed poorly with all other criteria sets. The level of experience of the rater (expert versus novice) with the earlier (Perley-Guze, DSM-III) and current (DSM-III-R) criteria did not influence the identification of cases by use of DSM-IV criteria. No racial effect was introduced by any of the criteria sets. CONCLUSIONS: The strategy for DSM-IV is an accurate and simpler method of diagnosing somatization disorder that does not require special expertise for proper use.

Adult↗
PubMed1994

The early events of oxygen and glucose deprivation: setting the scene for neuronal death?

It is generally thought that neuronal death caused by a reduction in oxygen or glucose supply, or both, occurs as a result of massive increases in the extracellular concentrations of excitatory amino acid neurotransmitters, particularly glutamate. A pertinent question is what happens before this increase, because measures which prevent extracellular accumulation of glutamate could have potential for clinical use in, for example, management of acute stroke. This article will review the major pathophysiological responses which occur up until the time of accumulation of glutamate. Withdrawal of energy substrate quickly leads to modest changes in membrane potential and intracellular and extracellular ion concentrations. Depression of action-potential-dependent synaptic transmission occurs a little later and might, in part, reflect actions of adenosine. Increases in the extracellular concentration of excitatory amino acids to neurotoxic levels take place only as membrane potential falls rapidly towards 0mV, coincident with massive changes in ion gradients.

Adenosine↗
PubMed1994

Cochlear pathology following chronic electrical stimulation of the auditory nerve: II. Deafened kittens.

The present study examines the effects of long-term electrical stimulation of the auditory nerve on cochlear histopathology and spiral ganglion cell survival in young sensorineural deafened cats. Eight kittens were deafened using kanamycin and ethacrynic acid, and implanted with bipolar or monopolar scala tympani electrodes. Following recovery from surgery the animals were unilaterally stimulated using charge balanced biphasic current pulses for 450-1730 hours over implant periods of up to four months. Charge densities varied from 0.6-0.9 microC.cm-2 geom. per phase for monopolar electrodes to 12-26 microC.cm-2 geom. per phase for the bipolar electrodes. Electrically-evoked auditory brainstem responses (EABRs) were periodically monitored during stimulation to confirm that the stimulus levels were above threshold, and to monitor any change in the response of the auditory nerve. Following completion of the stimulation program cochleae were prepared for histological examination. EABRs exhibited relatively stable thresholds for both stimulated and implanted, unstimulated control cochleae for the stimulus duration. While the growth in response amplitude as a function of stimulus current remained stable for the bipolar control and monopolar stimulated cochleae, the five cochleae chronically stimulated using bipolar electrodes exhibited a moderate to large increase in response amplitude. These increases were associated with a more widespread fibrous tissue response which may have altered the current distribution within these cochleae. Implanted control cochleae exhibited significantly less tissue response within the scala tympani. Importantly, we observed no statistically significant difference in the spiral ganglion cell density associated with chronic electrical stimulation when compared with unstimulated control cochleae. While the present study supports the safe application of cochlear implants in young profoundly deafened children, it does not corroborate previous studies that have reported electrical stimulation providing a trophic effect on degenerating auditory nerve fibres.

Analysis of Variance↗
PubMed1994

Treatment of acute gouty arthritis with intramuscular ketorolac tromethamine.

Nine consecutive patients presenting with acute gouty arthritis were treated with ketorolac 60 mg intramuscularly (IM). The average age was 58. Seven were male, and six were black. Pain was quantified in 6 of the patients using a 10-cm visual analog scale that the patients completed before and 30, 60, and 90 minutes after ketorolac administration. The mean pain score (+/- standard error of the mean) dropped from 6.43 (+/- 1.25), out of a possible 10, to 1.01 (+/- 35) (P < .01). There were no side effects of the medication. All of the patients were able to leave the treatment area satisfied with their treatment. None of the patients required crutches at discharge.

Acute Disease↗