Biomedical subjects
Publications and source records attributed to S Monroe.
The same urgency and intellect that America's teaching hospitals apply to saving lives is now also going into saving the institutions themselves. All across the country, academic medical centers are trying to figure out how to marry progress with profits. At the Duke University Medical Center, TIME visits the front line in the war between money and medicine.
In the study of the neural code for gustation, the relative sensitivity of a cell to a variety of taste stimuli is defined as its response profile. To study the construction of response profiles from incoming signals, electrophysiological responses to NaCl, HCI, quinine-HCl, sucrose and Na saccharin were recorded simultaneously in pairs of single cells: one in the nucleus of the solitary tract (NTS) and the other in the parabrachial nucleus of the pons (PbN), respectively the first and second synapses in the central pathway for gustation. Of 37 units recorded in the NTS and 32 in the PbN, 12 (32%) pairs showed evidence of functional connectivity. Although PbN responses were significantly larger than those in the NTS in general, no amplification of NTS activity was apparent among those units that were functionally connected. Analysis of NTS-PbN connectivity patterns suggests that PbN units receive input from NTS units with response profiles that are both similar and different from their own pattern of sensitivities. Further analysis suggests that the stimulus-selectivity of the response profile of a PbN unit may be determined by stimulus-selective input from NTS cells that show similar response profiles. However, input from NTS cells with response profiles different from their own appears to be non-stimulus-selective. Analysis of the organization of response profiles in the two structures suggests that the cells in both the NTS and PbN cannot be easily distinguished by their patterns of sensitivity to taste stimuli.
The production of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)/.OH in aqueous solutions of menadione and DMPO is enhanced by fluorescent room light. The formation of DMPO/.OH requires oxygen and water, is enhanced by superoxide dismutase, and occurs to a much smaller extent for benzoquinone than for menadione. This process is assigned as photo-initiated redox cycling of the menadione, which causes oxidation of DMPO to DMPO+. and reduction of oxygen to superoxide. DMPO+. reacts with water to produce DMPO/.OH. Although DMPO/.OOH was not observed in the menadione solutions, the possibility that some of the DMPO/.OH was produced by decomposition of DMPO/.OOH cannot be ruled out. There is no evidence for participation of hydroxyl radicals. Because benzosemiquinone is less readily oxidized than the semiquinone of menadione, redox cycling is less favorable for benzoquinone than for menadione and smaller quantities of DMPO/.OH are produced by photoexcitation of benzoquinone than of menadione.
Eleven outbreaks of acute gastroenteritis, eight of which were in nursing homes or retirement facilities, were reported in virginia during the winter of 1993-1994. Serum samples (four outbreaks) and stool samples (two outbreaks) from involved people were tested for human calicivirus (HuCV) infection by enzyme immune assays (EIAs) using recombinant Norwalk virus (rNV) and Mexico virus (rMX) capsid antigens and reverse transcription-polymerase chain reaction (RT-PCR). Of the 31 pairs of acute and convalescent serum specimens tested, 24 had a fourfold or more titer increase to rMX and 4 responded to rNV. In all four outbreaks, the geometric mean titers (GMTs) against rMX were significantly higher than those against rNV in the convalescent, but not in the acute phase of illness. The antibody response to rMX among these patients was also higher than to rNV (summary mean 32-fold increase vs. 0.7-fold increase, respectively, P < .001). Antigen was detected in 5 of 21 stool specimens tested by the rMX EIA, RNA in 12 of 17 stool specimens tested by RT-PCR, and small round structured virus (SRSV) particles in 12 of 21 by electron microscopy (EM); none were positive by the rNV EIA. Sequence analysis of the RT-PCR-amplified products from the viral RNA polymerase region revealed 92-93% amino acid identity with Snow Mountain agent (SMA), 86% with MX, 58-59% with NV, and 31-32% with Sapporo HuCV, suggesting that these viruses belong to the SMA HuCV genogroup.
A randomized, crossover study of 12 healthy volunteers was conducted with single, 1.5-g doses of mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), after oral and intravenous administration. During the intravenous infusion, phase systemic plasma clearance of MMF was approximately 10 L/min and the half-life (t1/2) was a few minutes. After oral administration, however, plasma MMF was below quantitation limits at all times. The plasma MPA profile of oral MMF showed a sharp peak at approximately 1 hour and a secondary peak at 8 to 12 hours. Mean apparent plasma t1/2 of MPA was similar for both routes (approximately 17 hours). The area under the concentration-time curve (AUC) from time 0 to 24 hours was statistically higher for intravenous than for oral administration, but total AUC showed statistical equivalence (80-120 rule), with mean bioavailability of MPA from oral administration of MMF estimated as 94.1% relative to the intravenous route. Total plasma AUC of mycophenolic acid glucuronide (MPAG), the sole metabolite of MPA, was four- to five-fold higher than MPA. Total 48-hour MPAG recovery in urine was statistically equivalent for the two routes and represented a mean of 70% of administered drug; corresponding MPA recovery was less than 1%. Renal clearance (ClR) values required transport mechanisms for MPAG, but not for MPA. The ClR of MPAG was statistically higher after intravenous administration than oral administration. MMF administered orally undergoes rapid, complete absorption and essentially complete presystemic deesterification. There was presystemic removal of MPA, but enterohepatic circulation compensated for the first pass loss. Renal metabolism of MPA also may have occurred.
The ability to apply and control the force and force velocity of mechanical stimulation is essential for the study of mechanoelectric transduction and adaptation processes. Silicon micromachining technology was used to produce miniature (20-70 microns wide) mechanical microprobes. Passive polysilicon, piezoresistive, force sensing elements were deposited onto the boron-doped epitaxial silicon and the individual devices were chemically etched from the bulk wafer. These microprobes display a linear force versus output voltage relationship. Stimulation forces up to 2 mN can be generated with a measurement resolution of 1.5 microN. The probes were mounted onto circuit board holders and their output sent to a proportional-integral controller which drives an electromagnetic actuator. By using this force-feedback control circuit coupled to a PC it is possible to define any stimulus wave form pattern and independently control and measure the actual stimulus force and velocity. A computer controlled 3-axis stepper motor (0.025 micron step capability) manipulator is used to position the silicon microprobe-actuator assembly relative to the mechanoreceptive field. Sensor feedback control coupled to the 3-axis stepper motor manipulator allows automatic touchdown control and/or preloading of the probe prior to stimulation. Three-dimensional topographic manipulator feedback position control allows automated receptive field mapping.
1. To date, there has been no quantitative, systematic, study of the electrophysiology of regenerating cold receptors. This study, therefore, examines the changes in cold-receptor neural activity following a circular wound (5 mm dia, 200 microns deep) on the surface of the rabbit cornea. This is a well studied wounding model, in which neural regeneration has been anatomically quantified. 2. Extracellular recordings were obtained from a total of 90 single cold fibers, at 1, 3, 10, 20, or 30 days following wounding. The adapting temperature was 35 degrees C in all experiments. Thermal sensitivity for each fiber was determined by using a series of temperature steps, 0.2 degree C ranging from 35 to 34 degrees C, and 2 degrees C steps ranging from 35 to 24 degrees C. The rate of temperature change ranged from 0.2 to 1 degree C/s. 3. At the adapting temperature, the tonic activity of the regenerating cold-fibers was not significantly different from normals. Conduction velocities for regenerating cold-fibers were slower on day 1 postwounding compared with normal fibers, 0.59 +/- 0.04 and 0.75 +/- 0.04 (SE) M/s, respectively, however, were within the normal range by day 30 postwounding, 0.72 +/- 0.06 M/s. 4. On day 1, sprouting fibers showed decreased responsiveness to cooling (P < 0.05). At days 3 and 10 postwounding, action potential rates in response to cooling were enhanced by 180-200% of normal (P < 0.05) and returned to preinjury values by 20 to 30 days postwounding.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Mechanisms of neural coding of gustatory stimuli were studied in the nucleus of the solitary tract (NTS), the first relay in the neural pathway for gustation, in anesthetized rats. Taste-responsive NTS units were identified as "relay" or "nonrelay" based on the electrophysiological response to electrical pulses delivered to the parabrachial nucleus of the pons (PbN), the second relay in the neural pathway for gustation. Coding mechanisms in each group were analyzed separately. 2. Taste responses to sapid solutions of NaCl (0.1 M), HCl (0.01 M), quinine HCl (0.01 M), sucrose (0.5 M) and Na-saccharin (0.004 M) were recorded in single units in the NTS. After gustatory stimulation, electrophysiological responses to electrical stimulation of the taste-responsive part of the ipsilateral PbN were recorded. A 0.2-ms pulse was delivered at 75-250 microA at a rates of 1, 25, 50 and 100 pps through a bipolar stainless steel electrode. An antidromic response was defined as a time-locked spike that occurred at a fixed latency after PbN stimulation that followed high stimulation frequencies. A collision test also was performed. 3. Of 42 taste-responsive NTS units, 19 (45%) were relay units, 22 (52%) were nonrelay and 1 unit was activated orthodromically by PbN stimulation. Latencies of evoked spikes ranged from 1.75 to 4.0 ms 2.1 +/- 0.2 ms (mean +/- SE, median, 1.75 ms). 4. Examination of general response characteristics revealed few differences among relay and nonrelay units.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Previous work has revealed a pervasive influence of the gustatory neocortex (GN) on the electrophysiological responses to taste in the parabrachial nucleus of the pons (PbN), the second synapse in the central pathway for gustation. Subsequent experiments have further suggested that direct projections from the GN to the PbN are not sufficiently dense to account for the widespread effects of cortical input. Because the main source of input to the PbN, i.e., the nucleus of the solitary tract (NTS), also receives input from the GN, the present experiment was conducted to test the hypothesis that changes in taste responses in the PbN after temporary elimination of GN input may be a normal reaction to altered input originating in the NTS. 2. Fourty-three taste-responsive neurons in the NTS were isolated initially in urethan-anesthetized rats. Single units were then classified as "relay" (n = 12) or "nonrelay" (n = 13) on the basis of their electrophysiological response to electrical shocks delivered to the taste-responsive portion of the PbN. After histological analyses, 18 units were classified as "unknown" because the PbN stimulating electrode was found to be outside the anatomically defined taste area in the pons. 3. Electrophysiological responses to sapid solutions of the NaCl (0.1 M), HCl (0.01 M), quinineHCl (0.01 M), sucrose (0.5 M), and Na-saccharin (0.004 M) were then recorded before and after recovery from infusions of procaineHCl into the GN. Both the ipsilateral and contralateral sides of the GN, in that order, received procaine infusions separated by a recovery period of at least 45 min. 4. Analysis of across-unit patterns of response was accomplished with the use of a vector space analysis. With this approach, the response of a given neuron to a given tastant is considered as a coordinate in n-dimensional space, where n is the number of neurons tested. The responses to each stimulus generate vectors whose length relates to the overall magnitude of response across the sample and whose relative directionality indicates similarity to other across-unit patterns. Measures derived from this type of analysis were used as input in a multidimensional scaling (MDS) analysis designed to summarize the organization of the across-unit patterns of response generated by the taste stimuli. This type of analysis creates a "taste space" in which similar across-unit patterns of response are placed close together and dissimilar patterns are placed far apart.(ABSTRACT TRUNCATED AT 400 WORDS)
A range of theories, including environmental, personality and cognitive theories, have suggested that loss may be a particularly critical form of stress in the etiology and expression of depression. The current study examines whether interpersonal depression predicted a unique clinical presentation and course in subjects with major depression. Subjects who became depressed following a severe interpersonal event were contrasted with two control groups: patients without antecedent stressors and patients with major non-interpersonal stressors. The hypothesized interpersonal subgroup was differentiated from the control groups only in the speed of treatment response. Proposals for future research are discussed.
The study of thermal transduction in neural tissues has been impeded by the lack of instrumentation able to generate complex, focal temperature variations. Specifically, we are interested in the study of neural thermal transduction within the cornea, with its homogeneous thermal conductivity and avascularity. We present a thermal signal generator probe that is capable of producing arbitrarily shaped bipolar (heating or cooling) thermal swings in a small volume of corneal tissue with which it is in contact. Heating and cooling of the probe tip are achieved by means of a Peltier effect thermoelectric device. The probe temperature, measured directly at the tip, is controlled using closed-loop control circuitry and waveform generation software on a host computer. Response characteristics of thermally sensitive C-fibers were investigated in an in vitro preparation of the rabbit cornea.
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Taste responses in units in the parabrachial nucleus of the pons (PbN) that receive direct projections from the gustatory neocortex (GN) were examined in the rat. Electrical stimulation was applied to the GN with bipolar stimulating electrodes. Time-locked responses to GN stimulation were observed in 19 of 62 (31%) taste-responsive units identified in the PbN. Of these, 17 units produced excitatory responses following GN stimulation and 2 units showed evidence of inhibition. No evidence of antidromic activation of PbN units was apparent. These results are consistent with descriptions of the anatomical projections from the GN to the PbN and demonstrate that some portion of taste-responsive neural elements within the PbN receive direct cortical input. PbN units that followed GN stimulation could not be distinguished from those that did not follow either by their spontaneous rates or their response profiles. These results suggest that axons from the GN do not select targets within the PbN based on the particular response properties.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.