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S Warren

Publications and source records attributed to S Warren.

At least 73 records · Page 4Linked to original sources
PubMed1989

Use of bioassay methods to evaluate mutagenicity of ambient air collected near a municipal waste combustor.

An ambient air sampling study was conducted around a municipal waste combustor; a primary goal was to develop procedures and methods to evaluate the emissions of organic mutagens resulting from incomplete combustion of municipal waste. The products of incomplete combustion from incineration include complex mixtures of organics, particularly polycyclic aromatic compounds, which are present after atmospheric dilution and cooling in emissions as semi-volatile or particle bound organic compounds. Combustion emissions are generally recognized as a potential cancer risk since they contain many carcinogenic and mutagenic polycyclic aromatic hydrocarbons. Analyzing such a complex mixture for the presence of even a few selected chemicals is difficult and provides risk information on only a fraction of the chemicals present. Bioassay methods, however, may be directly applied to evaluate the mutagenic and potential carcinogenic activity of the complex organics from combustion emissions. The Salmonella (Ames) assay was used to determine the mutagenicity associated with particles from ambient air collected near a municipal waste combustor. Dose-response data was generated, and mutagenicity concentrations were calculated to demonstrate the utility of bioassay in assessing the potential impact of emissions from municipal waste combustion. This phase of study quantified mutagenicity concentrations in ambient air but did not detect organic mutagens that could be attributed to incinerator emissions.

Air Pollutants, Occupational↗
PubMed1987

Multiple sclerosis in childhood: clinical profile in 125 patients.

Multiple sclerosis (MS) has its usual onset in early adult life (average age of 30 years), but age at clinical onset varies considerably. The implications of the age of onset on the clinical presentation and course of MS are unclear. This population-based retrospective study presents data from a group of 125 patients with onset of MS before age 16 years and can thus be considered as representative of MS occurring in childhood. It demonstrates that childhood MS is more frequent in girls, that it very often has a relapsing-remitting course, that initial bouts usually involve afferent structures of the central nervous system, that recovery from these is often complete, and that the pace of the disease is slow.

Adolescent↗
PubMed1987

Regulation of a metallothionein-rasT24 fusion gene by zinc results in graded alterations in cell morphology and growth.

We constructed fusion genes consisting of the mouse metallothionein I (MT) 5' region and the coding region of either the human H-ras gene (c-rasP3) or a mutated allele (c-rasT24); both ras genes lacked the initial (non-coding) exon and the first 30 bp of the non-coding region of the second exon. Transfection of Rat-1 cells produced foci only with pMT-rasT24, and selection in soft agar yielded clones in which MT-rasT24 expression was zinc-regulatable. In response to increasing concentrations of ZnSO4, these lines showed increasingly altered morphology (conversion to fusiform or spheroidal morphology), progressively higher maximal cell density, and an increasingly greater fraction of cells in the S + G2 + M portion of the cell cycle at high density. MT-rasT24 RNA levels in zinc-responsive lines were increased between 4- and 6-fold by the addition of ZnSO4 (final concentration = 100 microM) to the medium. Replating cells in the absence of zinc reversed the biological effects and resulted in reduction in MT-rasT24 RNA levels. Thus, graded alterations in phenotype result from increasing levels of MT-rasT24 gene expression.

Animals↗
PubMed1986

A population-based study of multiple sclerosis in twins.

Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.

Canada↗
PubMed1986

Objective classification of motion- and direction-sensitive neurons in primary somatosensory cortex of awake monkeys.

In order to classify movement-sensitive neurons in SI cortex, and to estimate their relative distribution, we have developed a new simple method for controlled motion of textured surfaces across the skin, as well as a set of objective criteria for determining direction selectivity. Moving stimuli were generated using 5 mm thick precision gear wheels, whose teeth formed a grafting. They were mounted on the shafts of low-torque potentiometers (to measure the speed and direction of movement) and rolled manually across the skin using the potentiometer shaft as an axle. As the grafting wheel was advanced, its ridges sequentially contacted a specific set of points on the skin, leaving gaps of defined spacing that were unstimulated. This stimulus was reproducible from trial to trial and produced little distention of the skin. Three objective criteria were used to categorize responses: the ratio of responses to motion in the most and least preferred directions [direction index (DI)], the difference between mean firing rates in the two directions divided by the average standard deviation [index of discriminability (delta'e)], and statistical tests. Neurons were classified as direction sensitive if DI greater than 35, delta's greater than or equal to 1.35 (equivalent to 75% correct discrimination by an unbiased observer), and firing rates in most- and least-preferred directions were significantly different (P less than 0.05). Good agreement was found between the three classification schemes. Recordings were made from 1,020 cortical neurons in the hand and forearm regions of primary somatosensory cortex (areas 3b, 1 and 2) of five macaque monkeys. Tangential motion across the skin was found to be an extremely effective stimulus for SI cortical neurons. Two hundred eighty six of 757 tactile neurons (38%) responded more vigorously to moving stimuli than to pressure or tapping the skin. One hundred twenty-one cells were tested with moving gratings and were classified according to their ability to differentiate movement in longitudinal and transverse directions. Responses to the moving gratings resembled those observed when stroking the skin with brushed, edges, or blunt probes. Three major types of firing patterns were found: motion sensitive, direction sensitive, and orientation sensitive. Motion-sensitive neurons (37%) responded to movement in both longitudinal and transverse directions with only slight difference in firing rates and interval distributions. Responses throughout the field were fairly uniform, and no clear point of maximum sensitivity was apparent. Direction-sensitive neurons (60%) displayed clear preferences for movement in one or more directions.4

Action Potentials↗
PubMed1986

Coding of the spatial period of gratings rolled across the receptive fields of somatosensory cortical neurons in awake monkeys.

In order to measure the texture coding capabilities of motion-, direction-, and orientation-sensitive neurons in SI cortex, we rolled wheels with surface milled gratings across their receptive fields. Gratings of spatial periods 0.8-9.6 mm were presented in pseudorandom order; each was tested 5-20 times in the distal, proximal, radial, and ulnar directions. Thirty eight cortical neurons were studied with three to eight different gratings in order to determine the effect of spatial period on neuronal firing rates. While all 38 cells had their firing rates modulated by motion of the gratings, only 11 neurons were able to distinguish changes in its spatial period. These cells had small receptive fields located on the hand. Most motion-sensitive neurons showed little effect of spatial period on firing rates and had relatively flat frequency response curves. One showed decreased firing to spatial periods over the range 0.8-6.4 mm; three others increased their firing rates over the range 0.8-3.2 mm, followed by a decline in activity to larger spatial periods. Direction- and orientation-sensitive neurons showed only minor changes in firing rates as a function of spatial period. Sixteen cells showed flat frequency response functions, three showed increased firing rates, and four decreased firing rates as spatial period of the grating increased. Direction and orientation preferences were maintained over the range 0.8-9.6 mm for all 23 neurons tested. Although four cells showed a drop in direction index (DI) as the spatial period was increased, none showed a loss of direction sensitivity, as DI was greater than 35 for all gratings tested. Two neurons showed increased firing to motion in the last-preferred direction and two others decreased firing in the best direction. The remaining 19 neurons showed parallel effects of texture in all directions. Some motion-sensitive neurons showed weak direction preferences when tested with fine gratings; these preferences disappeared with coarser gratings, due to increased responsiveness to motion in the least-preferred direction. These data demonstrate that movement-sensitive neurons do not require continuous trajectories across the skin but instead sequential activation of points aligned in a specific path. Cortical neurons appear capable of integrating information from points separated by up to 9 mm, as long as they are presented in the appropriate temporal sequence. Firing rates of direction- and orientation-sensitive neurons are more profoundly modified by changes in the direction of motion across the skin, and the temporal order of stimulation, than by alterations in the spatial characteristics of the moving stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

The somatosensory thalamus of the raccoon: properties of single neurons responsive to light mechanical stimulation of the forepaw.

These studies were undertaken to characterize the discharge properties of single neurons of the raccoon thalamic ventrobasal complex (VB) that respond to light mechanical stimulation of the glabrous surfaces of the forepaw. Microelectrodes were used to record the extracellular activity of 146 cells in anesthetized raccoons, and all neurons were histologically verified as falling within or along the boundaries of VB. Sixty-one neurons were tested for activation by electrical stimulaton of primarily somatosensory cortex. Of these, 88% were antidromically activated, 5% were synaptically activated, and the remaining 7% were unresponsive. Out of the total sample of 146 neurons, 136 had peripheral receptive fields (RFs) that were restricted to glabrous skin and revealed properties of modality and place-specificity predictable through knowledge of properties of primary mechanoreceptive afferents. Rapidly adapting (RA) neurons accounted for 77% of this modality-place-specific sample, while 19% were slowly adapting (SA), and 4% revealed properties indicative of input from Pacinian afferents (Pc). Absolute displacement thresholds were comparable for RA and SA neurons (range = 6-415 micron). Palmar RF areas (range = 3.3-328 mm2) were significantly larger than digital RF areas (range = 0.5-98.2 mm2). As defined by exponents (b) of power functions relating instantaneous discharge frequency to displacement ramp velocity, SA neurons formed a single, homogeneous group (range of values of b = 0.633-0.720). However, RA neurons fell into three distinct groups: those showing relatively steep functions (b = 0.559-0.938), those showing relatively flat functions (b = 0.146-0.334), and those showing discontinuous, or step, functions. A small number of neurons (7% of total sample) revealed "complex" properties, not predictable from knowledge of properties of primary afferents. These included five neurons whose RFs encompassed both glabrous and hairy skin, and several linear orientation, or "tactile edge," detectors. The present results, in conjunction with those of earlier studies of the raccoon dorsal column-medial lemniscal system, lead to the conclusion that different types of information transformation are emphasized at different levels of the system. Intramodality convergences (increases in RF area) occur primarily within the cuneothalamic relay, while changes in the coding of quantitative information are primarily a function of VB neurons. The appearance of linear orientation detectors--a type of tactile "feature detector"--indicates that the synthesis of information regarding complex spatial properties of stimuli has its beginnings within the somatosensory thalamus.

Animals↗
PubMed1985

Extra intestinal influences on exhaled breath hydrogen measurements during the investigation of gastrointestinal disease.

During the clinical investigation of patients with gastrointestinal disease by exhaled breath hydrogen measurement, the occurrence of inexplicable variations in recorded hydrogen values led to a search for extra intestinal factors which were capable of adversely influencing breath hydrogen concentration and impairing the diagnostic accuracy of the test. Serial breath samples were collected from normal subjects under a variety of conditions which might occur during routine clinical study, including, hyperventilation, exercise, cigarette smoking, and carbohydrate ingestion. Breath hydrogen concentrations were consistently reduced by hyperventilation (p less than 0.01) and exercise (p less than 0.05). Cigarette smoking, in contrast, caused a marked rise in measured breath hydrogen (p less than 0.01), as did oral carbohydrate (p less than 0.05). Prior bactericidal mouthwash abolished this carbohydrate associated rise, suggesting that the hydrogen was the result of fermentation by oropharyngeal bacteria. Because, in all instances, the changes in breath hydrogen were of sufficient magnitude to interfere with data interpretation, it is recommended that these factors are eliminated, whenever possible, from conditions of study.

Bacteria, Anaerobic↗
PubMed1985

Differential sensitivity to airpuffs on human hairy and glabrous skin.

To compare the relative sensitivities of glabrous and hairy skin, we measured reaction times (RTs) and detectability (d') of airpuffs delivered to the hairy dorsum and glabrous thenar eminence of the hand of six human subjects. In contrast to previous studies with mechanical contact stimuli, airpuffs applied to hairy skin were detected with equal or greater fidelity than airpuffs tested on glabrous skin. Mean RTs to three simultaneously applied airpuffs were significantly shorter (p less than .005) on hairy skin in five of six subjects, and in 74% of paired sessions; no significant difference in mean RTs was observed in 16% of the sessions. The superiority of hairy skin was less evident, however, when single airpuffs were tested, as significantly shorter responses were observed on only 45% of the paired sessions, and nearly identical responses on 38% of the sessions. Detectability of airpuffs (d'), which is independent of the value of RTs, was identical on hairy and glabrous skin at high airpuff intensities (1,600 dyn), and superior (n = 4) or equal (n = 2) on hairy skin with low airpuff intensities (800 dyn). Spatial summation was more pronounced on hairy than on glabrous skin. Three simultaneously presented airpuffs produced significantly shorter RTs than one airpuff in 85% of the paired sessions on hairy skin, but on only half of the sessions on glabrous skin. The spatial distribution of stimulus force was less important on hairy skin, as three low-intensity airpuffs produced the same or shorter RTs than one high-intensity airpuff. By contrast, on glabrous skin, detectability was significantly better when force was concentrated at a single point (1 X 1,600 dyn) than when diffused over a wide skin area (3 X 800 dyn). The enhanced sensitivity of hairy skin to airpuffs appears partially attributable to hair motion in the airstream. After hair removal by chemical depilation, detectability of airpuffs was reduced on hairy skin to a level equal to or below that on glabrous skin. Spatial summation on the depilated skin corresponded to that observed on the intact hairy skin, indicating that depilation did not abolish intensity discrimination, but rather lowered the overall sensitivity of hairy skin. These results show that hair follicle units form a very sensitive detection mechanism on hairy skin of the human hand, similar to that provided by Meissner's and Pacinian afferents in glabrous skin. These findings with airpuffs provide the first example of a tactile stimulus that is less effective for mechanoreceptors in glabrous skin than in hairy skin.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Distribution of cerebellar mossy fibers arising from neurons of the raccoon main cuneate nucleus.

The present study demonstrates that fibers originating in the raccoon main cuneate nucleus are not segregated in specific cortical regions of target cerebellar folia as reported in studies of the cat cuneocerebellar tract. This observation supports the hypothesis that exteroceptive and proprioceptive divisions of the raccoon cuneocerebellar tract do not exist as distinct structural entities. The findings of this study do not preclude the possibility that projections from the external and main cuneate nuclei are segregated within the cerebellar cortex on the basis of functional modality rather than nucleus of origin.

Animals↗
PubMed1984

Somatosensory thalamocortical connections in the raccoon: an HRP study.

In the North American raccoon (Procyon lotor), representations of the glabrous surfaces of the hand digits are found within separate subnuclei of the thalamic ventrobasal complex (VB) and on separate subgyri of the somatosensory cortex (SmI). In the present study, the retrograde transport of horseradish peroxidase from SmI to VB was utilized to study relationships between physiologically identified cortical subgyri and somatotopically corresponding thalamic subnuclei. Single large or multiple small injections confined to a single gyral crown led to retrograde labeling of large groupings of cells filling the entire VB subnucleus for the appropriate digit. In the aggregate, the regions of label appeared as thin, wedge-shaped sheets extended in the dorsoventral and anteroposterior dimensions, but flattened mediolaterally, and curving to form a laterally directed convexity; these appear to correspond to the lamellae of monkey VB described by others. These large injections led to labeling of approximately 80% of all large (18-30-micron diameter) cells within the lamella. Single, small, focal injections of a gyral crown led to variable amounts of labeling, ranging from an entire digital lamella to only a small focal cluster of cells. No evidence was obtained for the existence of anteroposteriorly extending "rods" of cells, as reported in primates. Finally, there was a sparse, but consistent labeling of cells of the posterior nuclear group (Po) following gyral crown injections. These results are in agreement with expectations based on prior electrophysiological studies of raccoon VB and SmI, as well as prior anatomical studies of thalamocortical relationships.

Animals↗
PubMed1984

Necrotizing enterocolitis and hemolysis associated with Clostridium perfringens.

Two newborns had necrotizing enterocolitis (NEC) and severe hemolytic anemia. Clostridium perfringens was identified in the peritoneal fluid of both infants, supporting the previous association of C perfringens with hemolysis reported in adult patients. Infants with NEC and hemolytic anemia should be aggressively treated with surgical debridement and high-dose parenteral penicillin G potassium. Similarly, Gram's stain of peritoneal fluid and resected bowel at laparotomy for NEC may be useful for early identification of the primary organism.

Anemia, Hemolytic↗
PubMed1984

Somatosensory evoked potentials (SEPs) and cortical single unit responses elicited by mechanical tactile stimuli in awake monkeys.

The origins of surface recorded evoked potentials have been investigated by combining recordings of single unit responses and somatosensory evoked potentials (SEPs) from the postcentral gyrus of 4 alert macaque monkeys. Responses were elicited by mechanical tactile stimuli (airpuffs) which selectively activate rapidly adapting cutaneous mechanoreceptors, and permit patterned stimulation of a restricted area of skin. Epidurally recorded SEPs consisted of an early positive complex, beginning 8-10 msec after airpuff onset, with two prominent positive peaks (P15 and P25), succeeded by a large negative potential (N43) lasting 30 msec, and a late slow positivity (P70). SEPs, while consistent in wave form, varied slightly between monkeys. The amplitude of the early positive complex was enhanced by increasing the number of stimulated points, or by placing the airpuffs in the receptive fields of cortical neurons located beneath the SEP recording electrode. SEP amplitude was depressed when preceded 20-40 msec earlier by a conditioning stimulus to the same skin area. Single unit responses in areas 3b and 1 of primary somatosensory (SI) cortex consisted of a burst of impulses, beginning 11-12 msec after the airpuff onset, and lasting another 15-20 msec. Peak unitary activity occurred at 12-15 msec, corresponding to the P15 wave in the SEP. No peak in SI unit responses occurred in conjunction with the P25 wave. Although SI neurons fired at lower rates during P25, the lack of any peak in SI unit responses suggests that activity in other cortical areas, such as SII cortex, contributes to this wave. Most unit activity in SI cortex ceased by the onset of N43, and was replaced by a period of profound response depression, in which unit responses to additional tactile stimuli were reduced. We propose that the N43 wave reflects IPSPs in cortical neurons previously depolarized and excited by the airpuff stimulus. Late positive potentials (P70) in the SEP had no apparent counterpart in SI unit activity, suggesting generation at other cortical loci.

Animals↗
PubMed1982

Emotional stress and the development of multiple sclerosis: case-control evidence of a relationship.

One hundred multiple sclerosis (MS) patients were compared to hospital controls, for life stress prior to onset age in the MS patients and controls did not differ on: the happiness of their childhood environment; their pre-onset age reaction to life's problems (relaxed and taking things in stride/tense or easily upset); or on their tendency to seek professional help with an emotional problem. However significantly more MS patients than controls reported that they were under unusual stress in the 2 yr period prior to onset age; and the MS patients described a greater number of stressful life situations, or single events, than the controls.

Adult↗