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Biomedical subjects

J L Mason

Publications and source records attributed to J L Mason.

At least 19 recordsLinked to original sources

A2B5+ and O4+ Cycling progenitors in the adult forebrain white matter respond differentially to PDGF-AA, FGF-2, and IGF-1.

Cycling glial progenitors reside within subcortical white matter of the mammalian adult forebrain. Either A2B5 or O4 expression defines two of the major classes of cycling progenitors. We examined the growth factor receptor profiles of these progenitor populations and their capability to proliferate and differentiate in response to PDGF-AA, FGF-2, and IGF-1. FGF-2 and IGF-1 enhance the acquisition of O1 by the O4+ progenitors, but have no significant effect on the acquisition of O4 and/or O1 by the A2B5+ progenitors. In contrast, PDGF-AA enhances the acquisition of O1 by the A2B5+ progenitors, while having no significant affect on the acquisition of O1 by the O4+ progenitors unless combined with FGF-2. In addition, PDGF-AA and FGF-2 promote the proliferation of A2B5+ progenitors, while having no mitogenic effect on the O4+ progenitors unless the two factors are combined with IGF-1. Interestingly, not all of the progenitors within the A2B5 or O4 populations express the same growth factor receptors nor respond similarly to growth factors. Thus, there are substantial differences between the two populations and heterogeneity within each of these populations may exist.

Animals↗

Interleukin-1beta promotes repair of the CNS.

Interleukin-1beta (IL-1beta) is a proinflammatory cytokine associated with the pathophysiology of demyelinating disorders such as multiple sclerosis and viral infections of the CNS. However, we demonstrate here that IL-1beta appears to promote remyelination in the adult CNS. In IL-1beta(-/-) mice, acute demyelination progressed similarly to wild-type mice and showed parallel mature oligodendrocyte depletion, microglia-macrophage accumulation, and the appearance of oligodendrocyte precursors. In contrast, IL-1beta(-/-) mice failed to remyelinate properly, and this appeared to correlate with a lack of insulin-like growth factor-1 (IGF-1) production by microglia-macrophages and astrocytes and to a profound delay of precursors to differentiate into mature oligodendrocytes. Thus, IL-1beta may be crucial to the repair of the CNS, presumably through the induction of astrocyte and microglia-macrophage-derived IGF-1.

Animals↗

Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre.

Exposure of young adult C57BL/6 mice to cuprizone in the diet initiated profound and synchronous demyelination of the corpus callosum, which was virtually complete by 4 weeks of exposure. Interestingly, even in the face of a continued exposure to cuprizone, there was spontaneous remyelination 2 weeks later. This remyelination preferentially involved smaller calibre axons. There was a suggestion of yet another cycle of demyelination (at 10 weeks) and remyelination (at 12 weeks), but by 16 weeks of exposure, the regenerative capacity was exhausted and the animals were near death. The relapsing-remitting pattern suggests this may be a useful model for certain human demyelinating disorders. In contrast to the above chronic model, the corpus callosum from mice exposed to cuprizone for only 6 weeks continued to remyelinate, with 67% of the axons being myelinated or remyelinated at 10 weeks. Interestingly, a significant reduction in the mean value for axonal diameter was observed during acute demyelination. Upon remyelination, however, the axonal calibre distribution returned to near-normal. In contrast, when mice were maintained on a cuprizone diet for 16 weeks, the mean value for axonal diameter was reduced to 60% of normal. These results provide further evidence that the interactions between oligodendrocytes and axons alter axonal calibre.

Amidines↗

Mature oligodendrocyte apoptosis precedes IGF-1 production and oligodendrocyte progenitor accumulation and differentiation during demyelination/remyelination.

We have documented changes in the oligodendrocyte population during demyelinating insult to the adult CNS. Feeding of cuprizone to adult mice led to apoptotic death of mature oligodendrocytes followed by profound demyelination of the corpus callosum. A regenerative response was initiated even during active demyelination. Oligodendrocyte progenitors have begun to proliferate and then accumulate within the lesion. Many of these cells may have migrated from the sub-ventricular zone and fornix before their accumulation in the demyelinating corpus callosum. The accumulation of differentiating oligodendrocyte progenitors was followed closely by the reappearance of mature oligodendrocytes and remyelination. Interestingly, an increase in IGF-1 mRNA was detected at Week 3 through Week 7, suggesting potential involvement in remyelination. Other factors, however, such as PDGF, NT3, FGF, jagged, and notch remained unchanged. These results suggest that the mature oligodendroglial population depleted by apoptosis is replaced by a newly formed oligodendroglial population derived from progenitors; these accumulate and seem to differentiate during remyelination.

Animals↗

Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination.

Metabolic insult results in apoptosis and depletion of mature oligodendrocytes during demyelination. To examine the role of insulin-like growth factor-1 (IGF-1) during acute demyelination and remyelination in the adult CNS, we exposed transgenic mice that continuously express IGF-1 (IGF-1 tg) to cuprizone intoxication. Demyelination was observed within the corpus callosum in both wild-type and IGF-1 tg mice 3 weeks after exposure to cuprizone. Wild-type mice showed significant apoptotic mature oligodendrocytes and a dramatic loss of these cells within the lesion that resulted in near complete depletion and demyelination by week 5. In contrast, the demyelinated corpus callosum of the IGF-1 tg mice was near full recovery by week 5. This rapid recovery was apparently caused by survival of the mature oligodendrocyte population because apoptosis was negligible, and by week 4, the mature oligodendrocyte population was completely restored. Furthermore, despite demyelination in both wild-type and IGF-1 tg mice, oligodendrocyte progenitors accumulated only in the absence of mature oligodendrocytes and failed to accumulate if the mature oligodendrocytes remained as demonstrated in the IGF-1 tg mice. These results suggest that IGF-1 may be important in preventing the depletion of mature oligodendrocytes in vivo and thus facilitates an early recovery from demyelination.

Acute Disease↗

Sensory fibers of the pelvic nerve innervating the Rat's urinary bladder.

Much attention has been given to the pelvic nerve afferent innervation of the urinary bladder; however, reports differ considerably in descriptions of afferent receptor types, their conduction velocities, and their potential roles in bladder reflexes and sensation. The present study was undertaken to do a relatively unbiased sampling of bladder afferent fibers of the pelvic nerve in adult female rats. The search stimulus for units to be studied was electrical stimulation of both the bladder nerves and the pelvic nerve. Single-unit activity of 100 L(6) dorsal root fibers, activated by both pelvic and bladder nerve stimulation, was analyzed. Sixty-five units had C-fiber and 35 units had Adelta-fiber conduction velocities. Receptive characteristics were established by direct mechanical stimulation, filling of the bladder with 0.9% NaCl at a physiological speed and by filling the bladder with solutions containing capsaicin, potassium, or turpentine oil. The majority (61) of these fibers were unambiguously excited by bladder filling with 0.9% NaCl and were classified as mechanoreceptors. All mechanoreceptors with receptive fields on the body of the bladder had low pressure thresholds (</=10 mmHg). Receptive fields of units with higher thresholds were near the ureterovesical junction, on the base of the bladder or could not be found. Neither thresholds nor suprathreshold responses could be related to conduction velocity. Bladder compliance and mechanoreceptor thresholds were influenced by the stage of the estrous cycle: both were lowest in proestrous rats and highest in metaestrous rats. Mechanoreceptors innervating the body of the bladder and the region near the ureterovesical junction showed two patterns of responsiveness to slow bladder filling. One group of units exhibited increasing activity with increasing pressure up to 40 mmHg, while the other group showed a peak in activity at pressures below 40 mmHg followed by a plateau or decrease in activity with increasing pressure. It is proposed that differences in stimulus transduction relate to the different response patterns. Thirty-nine units failed to respond to bladder filling. Eight of these were excited by intravesical potassium or capsaicin and were classified as chemoreceptors. The remaining 31 units were not excited by any stimulus tested. Chemoreceptors and unexcited units had both Adelta and C afferent fibers. We conclude that the pelvic nerve sensory innervation of the rat bladder is complex, may be sensitive to hormonal status, and that the properties of individual sensory receptors are not related in an obvious manner to the conduction velocity of their fibers.

Animals↗

Gene expression in brain during cuprizone-induced demyelination and remyelination.

When C57BL/6J mice, 8 weeks of age, received 0.2% Cuprizone in their diet, extensive demyelination in corpus callosum was detectable after 3 weeks, and there was massive demyelination by 4 weeks. As expected, the accumulation of phagocytically active microglia/macrophages correlated closely with demyelination. When Cuprizone was removed from the diet, remyelination was soon initiated; after 6 weeks of recovery, myelin levels were near-normal and phagocytic cells were no longer prominent. Steady-state levels of mRNA for myelin-associated glycoprotein, myelin basic protein, and ceramide galactosyltransferase were already profoundly depressed after 1 week of Cuprizone exposure and were only 10-20% of control values after 2 weeks. Unexpectedly, upregulation of mRNA for these myelin genes did not correlate with initiation of remyelination but rather with accumulation of microglia/macrophages. After 6 weeks of exposure to Cuprizone, mRNA levels were at control levels or higher-in the face of massive demyelination. This suggests that in addition to effecting myelin removal, microglia/macrophages may simultaneously push surviving oligodendroglia or their progenitors toward myelination.

Animals↗

Simple method for the analysis of tenoxicam in human plasma using high-performance liquid chromatography.

A simple, rapid and cost-effective method for the determination of tenoxicam in human plasma is described, using ketorolac as the internal standard. The extraction procedure utilised 5% zinc sulphate and methanol. A nucleosil C18 column and 35:65 acetonitrile-water phosphate buffered mobile phase (pH 2.8) were used, with ultraviolet detection at 355 nm. The assay was linear in the range 40 ng/ml-10 micrograms/ml, with recovery of extraction ranging from 87 to 102%. The intra- and inter-assay reproducibility had coefficients of variation of 3.9-7.7 and 1.6% respectively. The limit of detection for this method was 40 ng/ml.

Chromatography, High Pressure Liquid↗

Simple method for the determination of morphine and its active glucuronide metabolite in human plasma by high-performance liquid chromatography with electrochemical detection.

A simple method for the simultaneous determination of morphine and its pharmacologically active metabolite morphine-6-glucuronide in 0.5 ml human plasma is described. It is based on the method of Svensson [J. Chromatogr., 230 (1982) 427 and 375 (1986) 174], but uses only one solid-phase extraction cartridge prior to chromatography and only a 20-microliter injection volume. Mean recoveries of 90 and 85% for morphine and morphine-6-glucuronide, respectively, were obtained, the limit of detection being 2 nmol/l (at a signal-to-noise ratio of 3.0).

Chromatography, High Pressure Liquid↗

The role of arthroscopy in the problem total knee replacement.

Fourteen patients were retrospectively reviewed to examine the role of arthroscopy in the diagnosis and treatment of the problem total knee arthroplasty (TKA), and to define parameters for indications, techniques, and results. All patients had undergone a previous TKA, and postoperatively had problems with pain and/or range of motion. Routine evaluation failed to reveal sepsis or aseptic loosening. Arthroscopy was used to evaluate and treat certain specific conditions. The arthroscope was successful in removing loose bodies, correcting patella subluxation with an arthroscopic lateral release, excising a symptomatic pseudomeniscus, and releasing intraarticular adhesions to improve motion and relieve pain. The postoperative knee score improved 73%. Arthroscopy is a valuable tool to evaluate a painful TKA, and can be used to treat certain conditions that would otherwise require an arthrotomy. The rehabilitation time is easier on the patient and much quicker. Arthroscopy of a TKA does not compromise any future procedures. However, it remains a technically demanding procedure whose indications and expectations are still being defined.

Aged↗

Evaluation of a self-instructional method for improving doctor-patient communication.

The purpose of the project reported here was to develop and evaluate an educational intervention to improve the interviewing skills learned in medical school. Sixty fourth-year medical students in a required ambulatory care rotation were randomly selected and randomly assigned to one of four conditions. All students interviewed a simulated patient who presented with one of five main complaints, and the interview was videotaped. Students were assigned to a control group or to one of three intervention groups: viewing a self-instruction videotape, viewing and critiquing a videotape of their interview, or both of these activities. The students assigned to the control group did not participate in any educational interventions. At the end of the intervention period, the students again interviewed a simulated patient and were videotaped. The 120 videotaped interviews were reliably rated by a scoring system developed by the project team. The postintervention interviews conducted by students in the two groups that used the self-instruction videotape received significantly higher ratings than those in the control group. These results suggest that this self-instruction intervention can improve the interviewing skills of senior medical students.

Ambulatory Care↗

An assessment of entering freshman medical students' knowledge of and attitudes toward AIDS.

The purpose of this survey was to determine entering freshman medical student awareness of and attitudes toward AIDS. It is encouraging to find that, in general, students are well informed about AIDS before entering medical school; they have very real concerns about the possibility of contracting AIDS themselves as future care givers; and that they, in the final analysis, will consent to function as care givers to patients who have or may have AIDS while assuming responsibility to take appropriate precautions. It is important to stress that this survey reflects the pre-formed attitudes of entering freshman medical students. The University of Maryland School of Medicine is actively involved with the integration of AIDS education officially into the medical school curriculum. The results of this survey highlight the need for the inclusion of learning experiences designed to enhance physician/patient interaction skills when administering care to AIDS patients. It is believed that the acquisition of these desirable skills will generalize to better quality care for all patients. It is planned to administer the HIV/AIDS Questionnaire in a follow-up study to graduating seniors to assess their knowledge and attitudes toward AIDS. This will permit a comparison of attitude change among medical students, and an evaluation of newly implemented curricular changes.

Acquired Immunodeficiency Syndrome↗

Word and feature identification by profoundly deaf teenagers using the Queen's University tactile vocoder.

The experiments described are part of an ongoing evaluation of the Queen's University Tactile Vocoder, a device that allows the acoustic waveform to be felt as a vibrational pattern on the skin. Two prelingually profoundly deaf teenagers reached criterion on a 50-word vocabulary (live voice, single speaker) using information obtained solely from the tactile vocoder with 28.5 and 24.0 hours of training. Immediately following word-learning experiments, subjects were asked to place 16 CVs into five phonemic categories (voiced & unvoiced stops, voiced & unvoiced fricatives, approximants). Average accuracy was 84.5%. Similar performance (89.6%) was obtained for placement of 12 VCs into four phonemic categories. Subjects were able to acquire some general rules about voicing and manner of articulation cues.

Adolescent↗

Continuing evaluation of the Queen's University tactile vocoder. I: Identification of open set words.

Identification of open set words, by an experienced normal hearing subject using the tactile vocoder developed at Queen's University, was examined. The tactile vocoder filters and processes the acoustic waveform into 16 filter channels, each of which controls a vibrator on the skin surface. After acquiring a 250-word vocabulary through the tactile vocoder, the subject was presented with three sets of 1000 different open set words in three reception conditions. The percentages of words correctly identified in the tactile vocoder (TV), lipreading (L), and lipreading plus tactile vocoder (L + TV) conditions were 8.8, 39.4, and 68.7 percent respectively. Phonemic analysis of stimulus/response pairs revealed that 36.7, 64.9 and 85.5 percent of the phonemes were correctly identified in TV, L, and L + TV conditions, respectively, indicating that incorrect-response words often contained many correct phonemes. Also, syllabic stress of stimulus and response words was identical 88 percent of the time in the TV condition. Important information about speech was transmitted through the tactile vocoder.

Deafness↗