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D W Smith

Publications and source records attributed to D W Smith.

At least 145 records · Page 8Linked to original sources
PubMed1994

Similarity landscapes: a way to detect many structural and sequence motifs in both introns and exons.

When investigators undertake searches of DNA databases, they normally discard large numbers of alignments that demonstrate very weak resemblances to each other, retaining only those that show statistically significant levels of resemblance. We show here that a great deal of information can be extracted from these weak alignments by examining them en masse. This is done by building three-dimensional similarity landscapes from the alignments, landscapes that reveal whether an unusual number of individually nonsignificant alignments tend to match up to a particular region of the query sequence being searched. The power of the search is increased by the use of libraries consisting entirely of introns or of exons. We show that (1) similarity landscapes with a variety of features can be generated from both intron and exon libraries, using introns or exons as query sequences; (2) the landscape features are real and not a statistical artifact; (3) well-known protein motifs used as query sequences can generate various landscape features; and (4) there is some evidence for resemblances between short regions of sequence carried by introns and exons. One possible interpretation of these results is that both introns and exons may have been built up during their evolution from short regions of sequence that as a result are now widely distributed throughout eukaryotic genomes. Such an interpretation would imply that these short regions have common ancestry. Alternatively, the wide sharing of short pieces of DNA may reflect regions with particular structural properties that have arisen through convergent evolution. The similarity-landscape approach can be used to detect such widespread structural motifs and sequence motifs in the genome that might be missed by less-global searches. It can also be used in conjunction with algorithms developed for detecting significant multiple alignments by isolating promising subsets of the databases that can be examined in more detail.

Animals↗
PubMed1994

Arboviruses causing human disease in the Australasian zoogeographic region.

Over 65 arboviruses have been reported from countries in the Australasian zoogeographic region, but only a few have been implicated in human disease. These include the flaviviruses Murray Valley encephalitis (MVE), Kunjin (KUN), Kokobera (KOK), and dengue, particularly types 1 and 2; the alphaviruses Ross River (RR), Barmah Forest (BF), and Sindbis (SIN); and the bunyaviruses, Gan Gan and Trubanaman. In this paper recent epidemiological and clinical results pertaining to these viruses are reviewed, with major emphasis on MVE and RR viruses. The extensive early studies of Australian arboviruses have been reviewed by Doherty [49, 50], and their ecology and vectors more recently by Kay and Standfast [87]. In addition, the biology of MVE and KUN [113] and RR [87, 114] viruses have been the subjects of more detailed reviews. The Australasian zoogeographic region is defined as countries east of the Wallace and Weber lines, two hypothetical lines in the Indo-Australian archipelago where the fauna of the Australasian and Oriental regions meet. Seroepidemiological studies of human arboviral infections have suggested that the Japanese encephalitis flavivirus and the chikungunya alphavirus occur only in the Oriental region, whereas the related MVE and RR viruses, respectively, are restricted to the Australasian region [85, 148]. Serological results from Wallacea, the zone between the Wallace and Weber lines, are not so clear-cut [85]. This review is therefore restricted to countries east of Wallacea, specifically New Guinea and Australia.

Animals↗
PubMed1994

c-fos expression in hypothalamic neurosecretory and brainstem catecholamine cells following noxious somatic stimuli.

Noxious somatic stimuli elicit vasopressin secretion, an effect thought to result from activation of a facilitatory input from A1 catecholamine cells of the medulla oblongata. To better characterize the A1 cell response and effects on other neuroendocrine A1 projection targets, particularly within the paraventricular nucleus, we have now mapped c-fos expression in neurochemically identified catecholamine and neurosecretory cells following a noxious somatic stimulus. Unilateral hind paw pinch significantly increased c-fos expression in contralateral A1 cells whereas other brainstem catecholamine cell groups were unaffected. Expression of c-fos was also increased in the supraoptic nucleus, this effect being more pronounced for vasopressin than oxytocin neurosecretory cells and, as with A1 cells, primarily on the side contralateral to the stimulated paw. In contrast, the increase in the paraventricular nucleus was greater in oxytocin rather than in vasopressin cells. Additionally there was a significant rise in c-fos expression in medial parvocellular paraventricular nucleus cells of noxiously stimulated animals. Notably, the majority of tuberoinfundibular corticotropin-releasing factor cells are located in this medial parvocellular zone. These results are consistent with and expand on those previously reported from electrophysiological and anatomical studies. The finding of differing neurosecretory cell responses between supraoptic and paraventricular nuclei has interesting implications with regard to the afferent control of neurosecretory cell activity. For example, the substantially greater activation of supraoptic versus paraventricular nucleus vasopressin cells, despite being innervated by the same medullary noradrenergic cell group, raises the possibility of a differential input or differences in responsiveness. Furthermore, the activation of paraventricular nucleus parvocellular cells is consistent with suggestions that the A1 cell group provides an excitatory input to this population.

Animals↗
PubMed1994

Behavioral and electrophysiological responses to electrical stimulation in the cat. I. Absolute thresholds.

Estimates of electrical auditory brainstem response (EABR) thresholds are compared with behavioral thresholds for electrical stimulation in the same subject using identical stimuli and electrode configurations. Four cats were behaviorally trained to measure acoustic auditory thresholds using food as a reward in an operant reinforcement paradigm. One of the animals was then implanted, in an otherwise normal ear, with a scaled-UCSF multi-contact electrode array containing four intracochlear electrodes. Three animals were implanted with an electrode array containing eight intracochlear contacts and one extracochlear contact under the temporalis muscle following unilateral cochlear perfusion with 10% neomycin solution. Stimuli for the behavioral studies were single presentations of 200 us/phase biphasic current pulses. For the EABR studies, the same stimulus was presented at a rate of 32/s. In general, for the animal with the four-contact array and two of the three subjects with the eight-contact implant, changes in electrode configuration produced well-differentiated changes in threshold. For these three subjects, comparisons of behavioral and EABR thresholds for the majority of monopolar and bipolar electrode configurations tested showed excellent agreement (r2 = 0.88). Correlations between behavioral and EABR measures in these animals were comparable for bipolar and monopolar arrangements (r2 = 0.88 for bipolar and 0.87 for monopolar). For one subject with the eight-contact electrode, who showed similar monopolar and bipolar electrode behavioral thresholds for all tested electrode spacings or configurations, most EABR thresholds were substantially higher than, and poorly correlated with, behavioral thresholds (r2 = 0.15; r2 = 0.28 for monopolar arrangements, and r2 = 0.12 for bipolar arrangements).

Animals↗
PubMed1994

Pathogenesis of tuberculosis: pathway to apical localization.

We have examined the published work of investigators which dealt with the pathogenesis of tuberculosis, especially the following: the infective dose, the yield of bacilli from the primary lesion and primary complex, the predominant location of the minimal lesion, the hypotheses of a vulnerable region in the lung and the specific pathways (endogenous or exogenous) by which tubercle bacilli cause disease. More knowledge of the pathogenic pathway to tuberculosis would provide clues to the development of new vaccines and drug regimens that can intervene at a specific stage in the pathogenesis. Based on the examination of the literature on pathogenesis of human tuberculosis and our findings in a guinea-pig model of experimental airborne tuberculosis, we have proposed an hypothesis which integrates the endogenous and exogenous pathways to tuberculosis. This hypothesis is based on the following observations: 1. The infectious dose is very low, usually 1-5 tubercle bacilli. 2. The first implant can occur anywhere in the lungs. 3. The cavitary lesion, characteristic of tuberculous disease, is often located in the apical regions in the lungs. 4. Whereas the primary implant can occur anywhere in the lungs, for the progression from infection to disease, the tubercle bacilli must gain access to the 'vulnerable' regions in the apex of the lungs. Our hypothesis states that in areas of the world where there is a low risk of infection with tubercle bacilli low incidence of vaccination or sensitization to environmental mycobacteria, or high incidence of high virulent isolates, the virulent tubercle bacilli reach the vulnerable region via a bacillemia during the first infection. In areas of the world where there is a high risk of infection with tubercle bacilli, high incidence of vaccination or sensitization to environmental mycobacteria or a high incidence of low virulent isolates, the tubercle bacilli reach the vulnerable region via the airway, which requires repeated episodes of infection as the probability of a first implant occurring in the vulnerable regions is low.

Animals↗
PubMed1994

Mycobacterial infection in guinea pigs.

We described published reports of the chaos which exists in research concerning laboratory animal models for assay of tuberculosis (TB) vaccines and proposed a "rational animal model" as a solution to the problem. This animal model, an aerosol challenge model in guinea pigs, was recently applied to the problem of differences in growth characteristics of sputum isolates of low and high virulence. The same model was used to investigate the protective effect of high dose BCG given aerogenically. Based on studies in the guinea pig model of experimental airborne TB, and a review of the literature on pathogenesis of human TB, we described an "integrated model" for the pathogenesis of TB, a model which includes a role for both the endogenous reactivation and the exogenous reinfection pathways. Our hypothesis is that tubercle bacilli must be able to gain access to the "vulnerable region" in the lung apex in order to survive the effects of the CMI response. In endogenous reactivation TB (virulent tubercle bacilli), this access occurs via the bloodstream. Whereas in exogenous reinfection TB, access to the vulnerable region occurs via multiple exposures via the respiratory tract. Central to our perspective is the acceptance of the evidence that during first infection with virulent organisms, tubercle bacilli enter the bloodstream via the efferent lymphatics. We believe the hypotheses we have proposed have the potential to lead to a further increase in our knowledge of these mechanisms and are a prerequisite to studies aimed at the development of new vaccines.

Animals↗
PubMed1994

Initiation of rat vasopressin cell responses to simulated hypotensive hemorrhage.

Hypotensive hemorrhage is a major stimulus for vasopressin (VP) release, but in rats it is uncertain which receptors initiate this response. We have investigated this issue using transient occlusion of the inferior vena cava to simulate hypotensive hemorrhage. Single-unit recording experiments done in the supraoptic nucleus of pentobarbital-anesthetized rats demonstrated that severe caval occlusion, sufficient to drop mean arterial pressure (MAP) below 30 mmHg, excited 88% of putative VP neurosecretory cells and a similar proportion of putative oxytocin (OT) cells. Responsive VP cells increased their firing by 8.5 +/- 0.6 spikes/s within 11.2 +/- 0.8 s of the fall in MAP. This response was unrelated to the size of the fall in MAP and was unchanged by combined sinoaortic denervation (SAD) and vagal denervation, by T1 spinal section, or by administration of the angiotensin-converting enzyme inhibitor captopril, except that spinal section decreased the response latency. Moderate caval occlusion, sufficient to drop MAP to approximately 50 mmHg, did not excite any of the OT cells tested but did excite 65% of VP cells, causing a 3.8 +/- 0.3 spikes/s increase in firing after a delay of 9.0 +/- 1.3 s. This response was proportional to the size of the preceding fall in MAP, and after combined SAD and vagal denervation only 20% of VP cells still responded. Elimination of sinoaortic or vagal afferents alone had no effect on VP cell responses to moderate caval occlusion, except that SAD significantly increased the response latency. These data suggest that in rat the mechanisms that initiate the VP response to hypotensive hemorrhage depend on stimulus intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

A study of stairs in the housing of independently-living elderly people.

This survey study focuses on stairs in the homes of a substantial number of independently living elderly (60+) residents of a community in which there are mostly multistory houses and apartment buildings with stairs. While the majority could climb their stairs without problems, a substantial minority lived with stairs despite difficulty and even inability in climbing them. Most people were satisfied with their homes, and many were unwilling to admit that stairs were a present or potential problem. Most people, including most with stair problems, had no plans to move from their homes, however, a majority was willing to concede under questioning that stair-free living in a presently unplanned next home would be desirable. There is a plea that stairs be of increased concern in the housing of elderly people, and that there be increased planning for stair-free homes.

Activities of Daily Living↗
PubMed1994

Referral selection bias in the Medicare hospital mortality prediction model: are centers of referral for Medicare beneficiaries necessarily centers of excellence?

OBJECTIVE: Although the Health Care Financing Administration (HCFA) uses Medicare hospital mortality data as a measure of hospital quality of care, concerns have been raised regarding the validity of this concept. A problem that has not been fully evaluated in these data is the potential confounding effect of illness severity factors associated with referral selection and hospital mortality on comparisons of risk-adjusted hospital mortality. We address this issue. DATA SOURCES AND STUDY SETTING: We analyzed the 1988 Medicare hospitalization data file (MEDPAR). We selected data on patients treated at the two Mayo Clinic-associated hospitals in Rochester, Minnesota, and a group of seven other hospitals that treat many patients from large geographic areas. These hospitals have had observed mortality rates substantially lower than those predicted by the HCFA model for the period 1987-1990. STUDY DESIGN: Using the multiple logistic regression model applied by HCFA to the 1988 data, we evaluated the relationship between distance from patient residence to the admitting hospital and risk-adjusted hospital mortality. PRINCIPAL FINDINGS: Among patients admitted to Mayo Rochester-affiliated hospitals, residence outside Olmsted County, Minnesota was independently associated with a 33 percent lower 30-day mortality rate (p < .001) than that associated with residence in Olmsted County. When patients at Mayo hospitals were stratified by residence (Olmsted County versus non-Olmsted County), the observed mortality was similar to that predicted for community patients (9.6 percent versus 10.2 percent, p = .26), whereas hospital mortality for referral patients was substantially lower than predicted (5.0 percent versus 7.5 percent, p = < .001). After incorporation of the HCFA risk adjustment methods, distance from patient residence to the hospitals was also independently associated with mortality among the Mayo Rochester-affiliated hospitals and seven other referral center hospitals. CONCLUSIONS: The HCFA Medicare hospital mortality model should be used with extreme caution to evaluate hospital quality of care for national referral centers because of residual confounding due to severity of illness factors associated with geographic referral that are inadequately captured in the extant prediction model.

Aged↗
PubMed1993

Racial differences in the incidence of cardiac arrest and subsequent survival. The CPR Chicago Project.

BACKGROUND: Differences between blacks and whites have been reported in the incidence of several forms of cardiovascular disease, including hypertension and stroke. We examined racial differences in the incidence of cardiac arrest in a large urban population and in subsequent survival. METHODS: We collected data on all nontraumatic, out-of-hospital cardiac arrests in Chicago from January 1, 1987, through December 31, 1988, and compared the incidence and survival rates for blacks and whites. We examined the association between survival and race and seven other known risk factors by logistic-regression analysis. We computed incidence rates by coupling our data with U.S. Census population data. RESULTS: Our study population comprised 6451 patients: 3207 whites, 2910 blacks, and 334 persons of other races. The incidence of cardiac arrest was significantly higher for blacks than for whites in every age group. The survival rate after cardiac arrest was 2.6 percent in whites, as compared with 0.8 percent in blacks (P < 0.001). Blacks were significantly less likely to have a witnessed cardiac arrest, bystander-initiated cardiopulmonary resuscitation, or a "favorable" initial rhythm or to be admitted to the hospital. When they were admitted, blacks were half as likely to survive. The association between race and survival persisted even when other recognized risk factors were taken into account. We did not find important differences between blacks and whites in the response times of the emergency medical services. CONCLUSIONS: The black community in our study was at higher risk for cardiac arrest and subsequent death than the white community, even after we controlled for other variables.

Adolescent↗
PubMed1993

Australian encephalitis in Western Australia, 1978-1991.

OBJECTIVE: To review the various clinical manifestations of Murray Valley encephalitis (MVE) or Kunjin virus encephalitis in patients in Western Australia. DESIGN: Review of clinical records, 1978 to 1991. PATIENTS: Of 26 reported cases of Australian encephalitis, four were excluded from study because the patient's symptoms were not definitely associated with MVE virus or Kunjin virus infection. Two further cases of MVE were not reviewed as case records were not available. Of the remaining 20 patients, 18 had MVE and two had Kunjin virus encephalitis. RESULTS: Sixteen cases were in the Kimberley, a tropical region where the viruses are endemic. Four were in the subtropical Pilbara and Gascoyne regions. Thirteen of the 20 cases were in Aborigines, of whom 11 were children. The seven non-Aboriginal patients were adults. Seventeen of 20 cases were in males. The range of neurological disease and outcome was similar to that in previously reported cases, with convulsions, brainstem disease or respiratory failure in severe and fatal cases, and involvement of the spinal cord, cranial nerve or cerebellum in the moderate cases. One mild cases without neurological involvement was caused by Kunjin virus. CONCLUSIONS: The poor outcome in young Aboriginal children indicated that disease resulting from exposure early in life was more likely to be severe. The disease in adults, irrespective of facial background, was similar to that in cases reported previously from south-eastern Australia, but generally milder.

Adolescent↗
PubMed1993

High-frequency jet ventilation in children with the adult respiratory distress syndrome complicated by pulmonary barotrauma.

High-frequency jet ventilation (HFJV) was used in 29 children with severe ARDS complicated by pulmonary barotrauma (PBT). Treatment with HFJV was begun when PBT was progressing over a 24-h period while receiving conventional ventilation (CV). The mean (+/- SD) age was 0.95 +/- 1.21 years (range, 0.03-4 years). The most common diagnosis was viral pneumonia (n = 17); other diagnoses included aspiration pneumonitis (n = 4), bacterial pneumonia (n = 3), multiple trauma (n = 2), and near-drowning (n = 3). The Bunnell Life-Pulse ventilator was used at a rate of 240/min or 300/min, with inspiratory time of 0.02 sec. Twenty children survived (69%). Survivors and nonsurvivors had equal disease severity prior to HFJV as assessed by ventilator settings, alveolar-to-arterial oxygen tension gradient, oxygenation index, and blood gas values. Survivors had spent significantly less time on conventional ventilation prior to HFJV than nonsurvivors, with a mean (+/- SD) of 3.7 +/- 2.1 days vs 9.6 +/- 4.5 days, respectively (P < 0.05). Survivors underwent an average of 4.4 +/- 3.9 days of HFJV, which supported adequate gas exchange with lower airway pressures, and produced resolution or significant improvement in airleak on chest radiograph. In conclusion, we speculate that the application of HFJV early in the course of severe hypoxemic respiratory failure complicated by airleak, allows the reduction of airway pressures, thereby minimizing pulmonary barotrauma and allowing the lung to recover from the underlying insult. Further controlled evaluation of HFJV in this high risk group of patients is warranted.

Child, Preschool↗
PubMed1993

Neurochemical identification of fos-positive neurons using two-colour immunoperoxidase staining.

The discovery of immediate early genes (IEG) has provided neuroscientists with a new functional mapping technique. Labelling of neural tissue for the protein product of IEG provides an activity map with single-cell resolution. When combined with labelling for the chemical identity of the neuron, this provides a powerful tool for the investigation of specific cell populations along a neuraxis. Here we describe in detail a method which allows simultaneous bright-field visualization of neurochemically identified cells displaying increased IEG expression. This technique is evaluated in tissue from rats subjected to stimuli known to induce the expression of the IEG c-fos in various medullary catecholaminergic and hypothalamic neurosecretory cell groups. A 2-colour immunoperoxidase technique was used to visualize Fos, the nuclear protein product of c-fos, and the cytoplasmic antigens tyrosine hydroxylase (TH), phenylethanolamine N-methyl transferase (PNMT), oxytocin (OT) and vasopressin (VP). This involved simultaneous application of primary antibodies raised in different species followed by sequential application of appropriate biotinylated secondary antibodies and the avidin-biotin-peroxidase technique. Fos was visualized with nickel-intensified diaminobenzidine (Ni-DAB) in the first sequence while TH, PNMT, OT or VP were visualized with DAB alone, resulting in readily distinguishable black and amber reaction products, respectively. This dual immunoperoxidase technique is time saving compared to techniques using sequential application of primary antibodies and avoids the disadvantages associated with fluorescence techniques.

Animals↗
PubMed1993

BCG-induced protection in guinea pigs vaccinated and challenged via the respiratory route.

Since studies on cellular immune responses have demonstrated the role of the mucosal lymphoid system of the respiratory tract, we have studied responses obtained from the local respiratory route, compared to the systemic intradermal route, of BCG immunization. Guinea pigs vaccinated with different doses of BCG via both routes served to follow lymphoid cell proliferation, hilar lymph node and lung BCG clearance, lung granuloma formation and protection induced after virulent challenge. Results demonstrate that the aerogenic route of vaccination with BCG has no harmful side-effects for the host. In comparison with the intradermal route of vaccination, aerogenic vaccination with 10(5) BCG cfu induced higher local cellular immune responses and a substantially improved protective effect.

Administration, Inhalation↗
PubMed1993

Incidence of cardiac arrest: a neglected factor in evaluating survival rates.

STUDY OBJECTIVES: To add to our understanding of survival rates in out-of-hospital cardiac arrest studies, we examined the incidence of cardiac arrest in the published literature. We specifically estimated if incidence rates are uniform between communities and if any relationship exists between incidence and the reported survival rates. DESIGN: A retrospective study of nearly 100 cardiac arrest peer-reviewed articles from 1970 to 1989 was performed to identify reports that included rates for incidence and survival or provided sufficient data for the calculation of these rates. MEASUREMENTS AND MAIN RESULTS: We were able to obtain reported or calculated incidence and survival rates for 20 communities. Statistical analysis was performed to compare incidence rates between communities and examine the relationship across these 20 studies between incidence rates and reported survival rates. Incidence rates ranged significantly from 35.7 to 128.3 per 100,000, with a mean of 62. Survival rates ranged significantly from 1.6% to 20.7%. Incidence rates in these communities were negatively related to survival rates; that is, as the incidence rate increased, the survival rate decreased. We determined the regression curve that describes this inverse relationship. This nomogram can be used to identify survival/incidence rate combinations that are significantly above or below average. CONCLUSION: The marked variations in incidence and inverse relationship between incidence and survival could be due to true variation in risk among the populations reported (ie, some populations may be older or sicker than others). Also, different research methodologies may create artifactual differences among studies as standards for designing studies, terminology, and reporting data have not been uniform. Therefore, these findings may reflect methodological differences and true epidemiological differences among communities. Future reports should include a method, such as an incidence/survival nomogram, to analyze survival rates while taking into account the community incidence rate of cardiac arrest. Further analysis of incidence and survival is necessary to improve intersystem comparisons, a prerequisite to sound decisions about cardiac arrest treatment, health policy, and allocation of resources.

Heart Arrest↗
PubMed1993

Use of transesophageal echocardiography in the evaluation of traumatic aortic injury.

Indications for aortography following blunt chest trauma are broad and ill-defined. This study prospectively assessed the role of transesophageal echocardiography (TEE) in the evaluation of suspected aortic injury. We used both TEE and aortography to evaluate 69 patients with suspected thoracic aortic injury. The studies were performed and interpreted by staff radiologists and cardiologists. The mean study time for TEE was 27 minutes, whereas the mean study time for aortography was 76 minutes (p < 0.05). No complications occurred with either procedure. Both TEE and aortography revealed no evidence of aortic injury in 61 patients. There was one false-positive aortogram. TEE identified seven aortic injuries; four were confirmed by aortography. One patient underwent thoracotomy and aortic repair based on TEE findings alone. Aortograms yielded false-negative results for two patients; one injury was confirmed at thoracotomy, the other at autopsy. TEE accurately predicted the presence or absence of aortic injury in each case, for a diagnostic sensitivity and specificity of 100%. TEE can be performed safely and efficiently on the multiple-injury patient. We conclude that TEE is useful in the evaluation of suspected aortic injury.

Adult↗