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Biomedical subjects

W Young

Publications and source records attributed to W Young.

At least 73 records · Page 4Linked to original sources
PubMed1996

Independent depressive mechanisms of GABA and (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide on young rat spinal axons.

We compared the effect of GABA and the serotonin receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT) on compound action potential amplitudes, latency, and conduction velocity in the spinal cord isolated from young (eight to 13-day-old) Long-Evans hooded rats. Supramaximally activated conducting action potentials and extracellular K+ activity were recorded with microelectrodes from the cuneatus-gracilis fasciculi and corticospinal tract. In the cuneatus-gracilis fasciculi, 8-OH-DPAT (10(-4) M) significantly reduced response amplitudes by 26.1 +/- 10.3% (mean +/- S.D., P < 0.0001, paired t-test, n = 27) and increased latencies by 20.3 +/- 7.9% (P < 0.0001). GABA (10(-4) M) reduced/amplitudes by 31.7 +/- 15.0% (P < 0.0001, n = 28) and increased latencies by 6.1 +/- 5.4% (P < 0.0001). However, neither GABA nor 8-OH-DPAT significantly altered conduction velocities, suggesting that the latency shifts are due to changes in activation time and not conduction velocity. In cortical spinal tract, 8-OH-DPAT (10(-4) M) depressed response amplitudes by 18.9 +/- 9.6% (P < 0.05, n = 5), increased latencies by 23.3 +/- 7.2% (P < 0.0001), but reduced conduction velocities by 19.9 +/- 10.2%. GABA (10(-4) M) reduced amplitudes by 16.4 +/- 7.5% (P < 0.01, n = 5), increased latencies by 5.3 +/- 2.3% (P < 0.05), and did not change conduction velocities. Bicuculline or picrotoxin blocked the GABA effects but did not affect the 8-OH-DPAT effects on both tracts. The potassium channel blocker tetraethylammonium did not alter the 8-OH-DPAT effects. The Na+/K(+)-ATPase inhibitor ouabain (10(-6) M) markedly enhanced the depressive GABA effects from 27.9 +/- 12.0% to 49.4 +/- 24.5% (P < 0.01, n = 9), but had no effect on 8-OH-DPAT-mediated effects. These results suggest that GABA and serotonin agonists depress axonal excitability through different and independent mechanisms.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study.

The Multicenter Animal Spinal Cord Injury Study (MASCIS) adopted a modified 21-point open field locomotor scale developed by Basso, Beattie, and Bresnahan (BBB) at Ohio State University (OSU) to measure motor recovery in spinal-injured rats. BBB scores categorize combinations of rat hindlimb movements, trunk position and stability, stepping, coordination, paw placement, toe clearance, and tail position, representing sequential recovery stages that rats attain after spinal cord injury. A total of 22 observers from 8 participating centers assessed 18 hindlimbs of 9 rats at 2-6 weeks after graded spinal cord injury. The observers were segregated into 10 teams. The teams were grouped into 3 cohorts (A, B, and C), consisting of one experienced team from OSU and two non-OSU teams. The cohorts evaluated the rats in three concurrent and sequential sessions. After viewing a rat for 4 min, individual observers first assigned scores without discussion. Members of each team then discussed and assigned a team score. Experience (OSU vs. non-OSU) and teamwork (individual vs. team) had no significant effect on mean scores although the mean scores of one cohort differed significantly from the others (p = 0.0002, ANOVA). However, experience and teamwork significantly influenced reliability of scoring. OSU team scores had a mean standard deviation or discordance of 0.59 points, significantly less than 1.31 points for non-OSU team scores (p = 0.003, ANOVA) and 1.30 points for non-OSU individual scores (p = 0.001, ANOVA). Discordances were greater at the upper and lower ends of the scale, exceeding 2.0 in the lower (< 5) and upper (> 15) ends of the scale but were < 1.0 for scores between 4 and 16. Comparisons of non-OSU and OSU team scores indicated a high reliability coefficient of 0.892 and a correlation index (r2) of 0.894. These results indicate that inexperienced observers can learn quickly to assign consistent BBB scores that approach those given by experienced teams, that the scores are most consistent between 4 and 16, and that experience improves consistency of team scores.

Animals↗
PubMed1996

A new route of transmission for Escherichia coli: infection from dry fermented salami.

OBJECTIVES: This study evaluated the production of dry fermented salami associated with an outbreak of Escherichia coli O157.H7 infection in Washington State and California. METHODS: Facility inspections, review of plant monitoring data, food handler interviews, and microbiological testing of salami products were conducted. RESULTS: Production methods complied with federal requirements and industry-developed good manufacturing practices. No evidence suggested that postprocessing contamination occurred. Calculations suggested that the infectious dose was smaller than 50 E. coli O157:H7 bacteria. CONCLUSIONS: Dry fermented salami can serve as a vehicle of transmission for O157:H7 strains. Our investigation and prior laboratory studies suggest that E. coli O157:H7 can survive currently accepted processing methods.

Adult↗
PubMed1996

Devolution of hip and knee replacement surgery?

The objectives of this study were to assess trends in referral patterns for joint replacements (JRs) in Ontario between the fiscal year 1988/89 and the fiscal year 1993/94; to assess the redistribution of financial resources if services were provided to residents in the region where they reside; and to estimate the financial implications of the devolution of primary JRs from tertiary-care hospitals to community hospitals. Despite rapid growth in the provision of JRs, there was no significant change in their regional distribution. Community hospitals have increased their share of JRs at the expense of teaching hospitals. For hospitals located in Central east Ontario, the cost of providing JRs to nonresidents increased from $ 5.9 million in 1988/89 to $8.3 million in 1993/94. Devolution of primary JRs requires a minimum reallocation sum of $25.1 million, with potential cost savings of $4.3 million. Many obstacles limit the devolution and local provision of health care services, including modifications to referral patterns and the availability of provider expertise, especially when a substantial redistribution of resources is required. Better clinical data to evaluate outcomes and better patient-specific costing data are required. Devolution of services should be addressed in the context of appropriate institutional compensation for medical education.

Cost Allocation↗
PubMed1995

Lysine-based structure in the proregion of procathepsin L is the recognition site for mannose phosphorylation.

The recognition of lysosomal enzymes by UDP-GlcNAc: lysosomal-enzyme GlcNAc-1-phosphotransferase (phosphotransferase) is mediated by a protein structure on lysosomal enzymes. It has been previously demonstrated that lysine residues are required for phosphorylation of procathepsin L and are a common feature of the site on many lysosomal proteins. In this work, the procathepsin L recognition structure was further defined by identification of the region of the protein containing the structure and the critical lysine residues involved. Removal of the cathepsin L propeptide by low pH-induced autocatalytic processing abolished phosphorylation. The addition of either the purified propeptide or a glutathione S-transferase-propeptide fusion protein to the processed protein restored phosphorylation. Mutagenesis of individual lysine residues demonstrated that two propeptide lysine residues (Lys-54 and Lys-99) were required for efficient phosphorylation of procathepsin L. By comparison of the phosphorylation rates of procathepsin L, lysine-modified procathepsin L, and the procathepsin L oligosaccharide, lysine residues were shown to account for most, if not all, of the protein-dependent interaction. On this basis, it is concluded that the proregion lysine residues are the major elements of the procathepsin L recognition site. In addition, lysine residues in cathepsin D were shown to be as important for phosphorylation as those in procathepsin L, supporting a general model of the recognition site as a specific three-dimensional arrangement of lysine residues exposed on the surface of lysosomal proteins.

3T3 Cells↗
PubMed1995

Norepinephrine modulates excitability of neonatal rat optic nerves through calcium-mediated mechanisms.

We report that norepinephrine markedly increases excitability of neonatal rat optic nerves. To investigate the mechanisms of the norepinephrine-induced excitability increase, we studied isolated optic nerves from 42 neonatal (< three days old) and five adult (> three months old) Long-Evan's hooded rats. Norepinephrine (10(-6), 10(-5) and 10(-4) M) rapidly and reversibly increased the amplitude (mean +/- S.D.: 3.5 +/- 1.7%, 12.1 +/- 2.8% and 35.6 +/- 8.4%) of compound action potentials elicited by submaximal stimulation of neonatal optic nerves. The beta-1 adrenoceptor antagonist atenolol (10(-5) M) blocked the norepinephrine-induced increase in excitability but the alpha antagonist phentolamine (10(-5) M) did not. The beta agonist isoproterenol (10(-5) and 10(-4) M) increased response amplitudes (8.7 +/- 4.1% and 25.8 +/- 4.6%) but the alpha-1 agonist methoxamine and alpha-2 agonist clonidine did not. The beta antagonist propranolol blocked the isoproterenol effect. Replacing Ca2+ with Mg2+ or adding 0.8 mM of Cd2+ reversibly blocked the norepinephrine effects. Extracellular K+ concentrations did not change in optic nerves during norepinephrine application. Blockade of K+ channels with apamin (10(-6) M) or tetraethylammonium (10(-3) M) did not prevent the excitatory effects of norepinephrine. Adult rat optic nerves were insensitive to both norepinephrine (10(-4) M) and isoproterenol (10(-4) M). Our results indicate that norepinephrine increases neonatal optic axonal excitability through Ca(2+)-dependent mechanisms. The data suggest that the adrenoceptors are situated on the axons, that the excitability changes are not due to changes in extracellular K+ concentration or K+ channels sensitive to apamin or tetraethylammonium. The sensitivity of rat optic nerves to norepinephrine declined with age. Axonal adrenoceptors may play a role in optic axonal development and injury.

Adrenergic Agonists↗
PubMed1995

The impact of relocating vasectomies from hospital outpatient departments to non-hospital sites.

The objective of this study was to estimate the net dollar value of hospital resources that would be released if vasectomies currently performed in outpatient departments were performed in non-hospital sites. This article provides a descriptive analysis using administrative data for all non-hospital sites and all acute care institutions in Ontario performing vasectomies. It is based on 23,741 records of patients for whom a vasectomy was billed to the Ontario Health Insurance Plan (OHIP) in 1991-92. No substantial differences in the age distribution of patients were seen in non-hospital sites and those in hospital settings. About 75% of hospital outpatients received a local anesthetic that could have been administered in a non-hospital setting. Approximately $4.4 million in hospital resources would be released if 75% of all outpatient vasectomies were performed in non-hospital settings while OHIP billings would increase only by about $140,000. The demands on hospital funds available for patient activity could have been decreased by about $6.2 million, if this shift had occurred in 1991-92. Although opportunities exist in Ontario to release hospital resources by shifting vasectomies to non-hospital sites, current hospital and physician funding policies may represent a disincentive to shift activity away from institutional-based care.

Cost Savings↗
PubMed1995

Androgen receptor: an overview.

The action of androgens in regulating development and growth is mediated by androgen receptor (AR). AR is a member of the steroid hormone receptor superfamily, a class of receptors that function through their ability to regulate the transcription of specific genes. The AR is located in various target tissues, with its levels and activity altered with the onset of various cellular events (e.g., sexual development, malignant transformation). The modulation of AR levels occurs through a number of mechanisms, including transcription, and is regulated by various factors (e.g., androgens). The ability of AR to modulate gene transcription is through its interaction with specific DNA sequences located near or within the target gene promoter. The importance of the AR in reproductive physiology has been emphasized by the finding of AR mutations, leading to a variety of disorders, including testicular feminization syndrome. In this article, we review the structure and function of AR and the role AR plays in the function of the mammalian system.

Animals↗
PubMed1995

Relationship between strength qualities and sprinting performance.

The purpose of this study was to investigate the relationship between strength measures and sprinting performance, and to determine if these relationships varied for different phases of sprint running. Twenty (11 males and 9 females) elite junior track and field athletes served as subjects. Athletes performed maximum sprints to 50 m from a block start and time to 2.5, 5, 10, 20, 30, 40 and 50 m were recorded by electronic timing gates. The resultant forces applied to the blocks were obtained from two force platforms. Twenty-seven measures of strength and speed-strength (absolute and relative to bodyweight) were collected from the height jumped and the force-time curve recorded from the takeoff phase of vertical jumping movements utilizing pure concentric, stretch shortening cycle (SSC) and isometric muscular contractions. Pearson correlation analysis revealed that the single best predictor of starting performance (2.5 m time) was the peak force (relative to bodyweight) generated during a jump from a 120 degree knee angle (concentric contraction) (r = 0.86, p = 0.0001). The single best correlate of maximum sprinting speed was the force applied at 100 ms (relative to bodyweight) from the start of a loaded jumping action (concentric contraction) (r = 0.80, p = 0.0001). SSC measures and maximum absolute strength were more related to maximum sprinting speed than starting ability. It was concluded that strength qualities were related to sprinting performance and these relationships differed for starting and maximum speed sprinting.

Adolescent↗
PubMed1995

Rates of tibial osteotomies in Canada and the United States.

This study determined the temporal trends and factors associated with the rates of performance of tibial osteotomies from 1985 to 1990 in Ontario, Canada and the United States. The Health Care Financing Administration, Ontario Health Insurance Plan, and National Hospital Discharge Survey databases were used to determine the number of osteotomies from 1985 to 1990. Osteotomy rates decreased in both countries approximately by 11% to 14% per year in patients 65 years and older and by 3% to 4% per year in patients younger than 65 years. Men received twice as many osteotomies as women in both countries. In the United States, the average rate of tibial osteotomies was 2 to 3 times lower than in Ontario.

Age Factors↗
PubMed1994

Elevation and clearance of extracellular K+ following graded contusion of the rat spinal cord.

The elevation and clearance of extracellular potassium concentration ([K+]e) were studied following graded contusion injury of the rat thoracic spinal cord. Animals were anesthetized, paralyzed, laminectomized at T9-T10, and then artificially ventilated. A 10-g rod was dropped 1.25, 2.5, or 5 cm onto the dorsal thoracic cord with the dura intact. After impact, and incision of the dura-arachnoid and pial membranes, double-barreled, potassium-selective microelectrodes were inserted midway between the midline and lateral edge of the cord. For all three injury levels, the elevation of [K+]e was greatest within the first 1000 microns from the dorsal surface. In 50 g-cm injuries, increasing [K+]e was sometimes observed between 250 and 1000 microns; however such gradients were not typically observed in 25 and 12.5 g-cm injuries. Measured at 3-7 min after injury, the mean peak elevations of [K+]e were significantly different, measuring 13 +/- 2.4, 27 +/- 5.5, and 44 +/- 4.2 mM following 12.5, 25, and 50 g-cm contusions, respectively. The exponential half-times of [K+]e clearance averaged 5.8 +/- 1.0, 9.2 +/- 1.8, and 17 +/- 5.7 min for the same respective injury levels. These results indicate that elevation of [K+]e following traumatic injury to the spinal cord is a graded phenomenon, dependent on the energy of impact. This finding is consistent with a mechanism in which simple mechanical injury of cell membranes is the proximate cause of potassium release.

Animals↗
PubMed1994

Effect of mianserin on locomotory function after thoracic spinal cord hemisection in rats.

To study the role of serotonin (5-HT) in spinal cord injury, we observed the effects of mianserin (a 5-HT1c and 5-HT2 receptor antagonist) on rat locomotory function after thoracic spinal cord hemisection. Three groups of rats were studied: sham, A, and B. The sham group (n = 4) received laminectomy and a 3-day course of mianserin (5 mg/kg ip); group A (n = 12) had laminectomy, hemisection, and weekly 3-day courses of saline or mianserin; group B (n = 12) was identical to group A except that the rats received saline. The rats were evaluated every other day for 6 weeks using a 0-14 point scale. Hemisection markedly reduced mean ipsilateral hindlimb scores from 14.0 to 4.0 +/- 0.4 and 4.6 +/- 0.2 (mean +/- standard deviation) in groups A and B, respectively. The saline-treated rats recovered to scores of 9 or 10 by Day 7, 12 or 13 by Day 14, and normal by Day 21. Mianserin significantly but transiently depressed mean locomotory scores, from 12.1 +/- 0.6 to 10.0 +/- 0.4 (P < 0.05, Mann-Whitney U test) in the second week and from 14.0 +/- 0.0 to 12.1 +/- 0.6 (P < 0.05, Mann-Whitney U test) in the fourth week after hemisection. Locomotory scores of mianserin-treated rats did not differ significantly from control saline-treated rats by 7 days after treatment. Immunohistological studies of the spinal cords revealed a marked reduction of 5-HT-containing terminals in ipsilateral but not contralateral lumbosacral cord by 2 weeks after hemisection. By 4 weeks after hemisection, 5-HT-immunoreactive fibers and terminals partly returned to the ipsilateral lumbosacral cord, corresponding temporally with locomotory recovery. Thus, 5-HT may play a role in recovery after hemisection. Anti-serotonergic drugs should be cautiously administered to patients recovering from spinal cord injury.

Analysis of Variance↗
PubMed1994

Excitatory and inhibitory effects of serotonin on spinal axons.

We studied the effects of serotonin on compound action potentials in dorsal columns isolated from young (nine to 13 days old) rats. Conducting action potentials were activated by submaximal (50%) and supramaximal constant current electrical stimuli and recorded with glass micropipettes. At 10 microM and 100 microM concentrations, serotonin significantly increased mean action potential amplitudes by 9.6 +/- 6.5% (+/- S.D., P < 0.05) and 16.6 +/- 12.2% (+/- S.D., P < 0.005), respectively. Likewise, 10 microM and 100 microM of quipazine (a serotonin2A agonist) increased the amplitudes by 9.6 +/- 2.5% (+/- S.D., P < 0.0005) and 37.7 +/- 8.7% (+/- S.D., P < 0.0005), respectively. In contrast, 10 microM and 100 microM concentrations of 8-hydroxy-dipropylaminotetralin-hydrobromide (a serotonin 1A agonist) reduced axonal excitability by -9.4 +/- 5.5% (+/- S.D., P < 0.05) and -32.9 +/- 10.6% (+/- S.D., P < 0.0005), respectively. At 50 microM concentration, mianserin (a serotonin2A and serotonin2C antagonist) eliminated the excitatory effects of 100 microM quipazine dimaleate. The combination of 50 microM mianserin and 100 microM serotonin reduced action potential amplitudes by -5.6 +/- 4.9% (+/- S.D., P < 0.05). These results suggest that serotonin1A and serotonin2A receptor subtypes are present on spinal dorsal column axons. These two receptor subtypes have opposing effects on axonal excitability. The ratios and sensitivities of these two axonal receptor subtypes may modulate axonal excitability in rat dorsal column axons and have important implications for both development and injury of axons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Respiratory distress following cesarean section: cryptic presentation of bladder injury.

A case documenting the development of massive urinary ascites with associated pleural effusions and respiratory compromise due to an unrecognized cystotomy at the time of a tertiary low-vertical cesarean section is reported. The diagnosis was supported by elevated levels of serum blood urea nitrogen and creatinine and a peritoneal fluid to plasma creatinine ratio of 3:1. Imaging studies confirmed urinary extravasation into the peritoneum as well as bilateral pleural effusions and ascites. Primary intervention was to improve the patient's respiratory status and then to surgically repair the bladder wound.

Adult↗