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D W Smith

Publications and source records attributed to D W Smith.

At least 55 records · Page 3Linked to original sources
PubMed2000

Characterization of the dopamine defect in primary cultures of dopaminergic neurons from hypoxanthine phosphoribosyltransferase knockout mice.

Lesch-Nyhan disease (LND) is an X-linked metabolic disorder caused by lack of activity of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT) and characterized by hyperuricemia and debilitating neurological manifestations. The mechanisms underlying the neuropathology are not well understood and the principal neurochemical lesion characterized to date is a deficiency of the dopamine system in the basal ganglia. To facilitate the study of mechanism(s) by which HPRT deficiency causes the dopamine defect, we have compared the survival and dopamine phenotype of primary cultures of dopamine neurons derived from HPRT-deficient mice with the dopaminergic neurons from wild-type mice. The survival of dopaminergic neurons from both sources was promoted to an equal extent by glial cell line-derived neurotrophic factor (GDNF), a potent survival factor for dopamine neurons in vitro. Although the survival of the HPRT-deficient neurons was indistinguishable from that of cells derived from wild-type counterparts, the HPRT-deficient cells demonstrated a persistent deficiency of dopamine content and dopamine uptake with increasing neuritic differentiation, indicating that GDNF does not restore the normal phenotype in HPRT-deficient dopamine neurons despite its well-known protective and regenerative properties in several neurodegeneration models. Nevertheless, the demonstration that GDNF trophic support promotes the survival of these dopaminergic neurons will facilitate gaining a better understanding of the neuropathological mechanisms of LND by allowing a more extensive analysis of the cells central to the Lesch-Nyhan phenotype, the dopaminergic neurons of the basal ganglia.

Animals↗
PubMed2000

Heredity and the autonomic nervous system in human hypertension.

Because the complex phenotype of human hypertension is at least in part genetically determined, how individual genes ultimately contribute to the disease is not well understood. By contrast, intermediate phenotypes are traits associated with complex disease, but which may display simpler genetic properties such as greater heritability, more consistent and earlier penetrance and bimodality, and may suggest particular candidate susceptibility genes. Because autonomic nervous system activity is altered in hypertension, we examined biochemical, physiologic, and pharmacologic autonomic traits that fulfill at least some of these properties. Such biochemical, physiologic, or pharmacologic autonomic traits may be especially valuable as phenotypic anchor points in linkage or association studies probing the genetic basis of human hypertension.

Autonomic Nervous System↗
PubMed2000

Delay in disclosure of childhood rape: results from a national survey.

OBJECTIVE: This study sought to gather representative data regarding the length of time women who were raped before age 18 delayed prior to disclosing such rapes, whom they disclosed to, and variables that predicted disclosure within 1 month. METHOD: Data were gathered from 3,220 Wave II respondents from the National Women's Study (Resnick, Kilpatrick, Dansky, Saunders, & Best, 1993), a nationally representative telephone survey of women's experiences with trauma and mental health. Of these, 288 retrospectively reported at least one rape prior to their 18th birthday. Details of rape experiences were analyzed to identify predictors of disclosure within 1 month. RESULTS: Fully 28% of child rape victims reported that they had never told anyone about their child rape prior to the research interview; 47% did not disclose for over 5 years post-rape. Close friends were the most common confidants. Younger age at the time of rape, family relationship with the perpetrator, and experiencing a series of rapes were associated with disclosure latencies longer than 1 month; shorter delays were associated with stranger rapes. Logistic regression revealed that age at rape and knowing the perpetrator were independently predictive of delayed disclosure. CONCLUSIONS: Delayed disclosure of childhood rape was very common, and long delays were typical. Few variables were identified that successfully predicted disclosure behavior, but older age and rape by a stranger were associated with more rapid disclosure. This suggests that the likelihood of disclosure in a given case is difficult to estimate, and predictions based on single variables are unwarranted.

Child↗
PubMed2000

Topical aminoglycoside ototoxicity: attempting to protect the cochlea.

Cochlear damage following topical application of aminoglycoside antibiotics to the round window membrane is a recognized phenomenon in both animal experiments and clinical reports. The authors have recently reported the ability of the free radical scavenging agent, alpha lipoic acid, to protect against the cochleo-toxic side effects of systemically administered aminoglycoside antibiotics. This study attempts to determine if the protective effect of this free radical scavenging agent is also seen following topical aminoglycoside application. Animals were implanted with osmotic pumps which delivered 2.5 microl/h solution of either neomycin 5% or neomycin plus alpha lipoic acid (50 mg/ml). Control animals received normal saline solution. Drug solutions were presented directly to the round window membrane over a 7-day period. Auditory sensitivity was monitored using compound action potentials (CAPs) of the auditory nerve recorded through an implanted chronic electrode terminating at the round window. Sixteen animals were entered into the study and randomized to one of the above groups. All animals receiving neomycin solution, with or without alpha lipoic acid, maintained normal thresholds for the first 3 days of the treatment period. Animals receiving neomycin solution alone experienced profound and rapid deterioration in auditory sensitivity, which was maximal by day 6. Animals receiving neomycin plus alpha lipoic acid also experienced significant cochlear damage; however, the rate of deterioration was slower than that seen in the group receiving neomycin alone. All control animals receiving saline maintained good hearing thresholds throughout the treatment period.

Administration, Topical↗
PubMed2000

Early diagnosis of Murray Valley encephalitis by reverse transcriptase-polymerase chain reaction.

A 4-year-old aboriginal boy developed encephalitis due to Murray Valley encephalitis virus (MVE) following an earlier infection with Kunjin virus (KUN). The illness was severe, resulting in cerebral atrophy and profound physical and intellectual disability. The earlier KUN infection complicated his serological profile and delayed antibody responses to MVE. By contrast, the reverse transcriptase-polymerase chain reaction (RT-PCR) assay detected MVE in serum 3 days after the onset of illness and 4 days before the appearance of MVE-specific IgM. We suggest that MVE-specific RT-PCR provides rapid and specific diagnosis of MVE and should be used more widely for the diagnosis of acute viral encephalitis in cases originating from flavivirus endemic areas.

Antibodies, Viral↗
PubMed2000

Decreased antimicrobial resistance following changes in antibiotic use.

The widespread use of perioperative antibiotic prophylaxis makes surgical procedures an important component of overall antibiotic use. Attempts to reduce costs and limit the emergence of resistance among pathogenic bacteria by altering antibiotic use must therefore encompass surgical prophylaxis. Several recent reports have linked the use of third-generation cephalosporins with beta-lactam resistance in gram-negative bacteria and with vancomycin resistance in Enterococcus. Fortunately, susceptibility can often be restored by replacing third-generation cephalosporins with drugs that are less likely to foster resistance; a penicillin/beta-lactamase inhibitor combination is often a suitable substitute. An antibiotic resistance management program can effect the type of changes in antimicrobial use necessary to forestall or reverse an outbreak of resistant pathogens. Such a plan was implemented at Methodist Hospital, Indianapolis, Indiana, in 1995. Piperacillin/tazobactam (in combination with an aminoglycoside) was added to the formulary, primarily as empiric therapy, replacing the use of third-generation cephalosporins such as ceftazidime. Following this change, the prevalences of vancomycin-resistant Enterococcus, methicillin-resistant Staphylococcus aureus, and other resistant gram-negative bacilli were all reduced. As this effective formulary change shows, appropriate changes in antibiotic drug, dosage, and administration route can limit the emergence of resistance and ultimately lower costs.

Anti-Bacterial Agents↗
PubMed2000

Psychophysical correlates of contralateral efferent suppression. I. The role of the medial olivocochlear system in "central masking" in nonhuman primates.

An extensive physiological literature, including experimental and clinical studies in humans, demonstrates that activation of the medial olivocochlear (MOC) efferent system, by either contralateral sound or electrical stimulation, can produce significant alterations in cochlear function and suggests a role for the MOC system in influencing the auditory behavior of binaural hearing. The present data are from psychophysical studies in nonhuman primates which seek to determine if the noted physiological changes in response to contralateral acoustic stimulation have a perceptual counterpart. Four juvenile Japanese macaques were trained to respond to the presence of 1-s sinusoids, presented to the test ear, in an operant reinforcement paradigm. Thresholds were compared for frequencies ranging from 1.0 to 4.0 kHz in quiet, with thresholds measured when continuous, two octave-band noise, centered on the test tone frequency, was presented in the contralateral ear. Contralateral noise was presented at levels of 10-60 dB above detection threshold for the test-tone frequency. While some variability was evident across subjects, both in the frequency distribution and magnitude (as a function of contralateral noise level), all subjects exhibited an increase, or suppression of thresholds in the presence of contralateral noise. On average, thresholds increased systematically with contralateral noise level, to a peak of 7 dB. In one subject, the threshold increase seen with contralateral noise was significantly reduced when the MOC was surgically sectioned on the floor of the IVth ventricle. The characteristics of the measured shifts in behavioral thresholds, in the presence of contralateral noise reported here, are qualitatively and quantitatively similar to both efferent physiological suppression effects and psychophysical central masking threshold shifts which have been reported previously. These data suggest that at least some aspects of "central masking" are efferent-mediated peripheral processes, and that the term "central masking" may be incorrect.

Acoustic Stimulation↗
PubMed2000

Comparison of conduct-disordered behavior in crack-dealing versus nondealing juvenile offenders.

Currently, little research has investigated psychosocial functioning among juvenile crack dealers, and there appear to be few studies comparing dealers to nondealing juvenile offenders. The current study examined whether juvenile crack dealers display more severe conduct-disordered behavior than their nondealing delinquent peers. The records of 130 adolescent males committed to a residential training school were studied. Analyses indicated that crack dealers were younger when first arrested, had more arrests and commitments, and met more DSM-III-R conduct-disorder criteria than their nondealing delinquent peers. In addition, the DSM-III-R conduct-disorder criteria met by dealers were more severe, and dealers were more likely to be rearrested within six months following release. Overall, significant differences between crack dealers and nondealing juvenile offenders were found; dealers displayed a more delinquent history and a more serious and violent conduct disorder than their nondealing yet delinquent peers.

Adolescent↗
PubMed2000

Murray Valley encephalitis in Western Australia in 2000, with evidence of southerly spread.

We describe the epidemiological and clinical features of human Murray Valley encephalitis (MVE) and Kunjin (KUN) virus infections in Western Australia (WA) during March to July 2000. A case series was performed. For laboratory-confirmed cases, travel histories and clinical details were collected from patients, family members, friends or treating physicians. Surveillance data from the sentinel chicken program and climatic conditions were reviewed. Nine encephalitic cases of MVE were recorded. Eight were non-Aboriginal adults (age range, 25 to 79 years; 5 male, 3 female) and 1 was an Aboriginal boy. Four cases acquired infection in the Murchison and Midwest regions of WA from which no human cases of MVE have been reported previously. One of the 9 cases was fatal and 3 had severe neurological sequelae. Five non-encephalitic infections were also recorded, 3 MVE and 2 KUN. Encephalitis caused by MVE virus remains a serious problem with no improvement in clinical outcomes in the last 25 years. Excessive rainfall with widespread flooding in the northern two-thirds of WA provided ideal conditions for mosquito breeding and favoured southerly spread of the virus into new and more heavily populated areas. Surveillance in WA with sentinel chickens and mosquito trapping needs expansion to define the boundaries of MVE virus activity. To enable timely warnings to the public, and to institute mosquito control where feasible, continued surveillance in all Australian areas at risk is indicated.

Adult↗
PubMed2000

Role of DNA methylation at GATC sites in the dnaA promoter, dnaAp2.

DnaA protein is required for the initiation of DNA replication at the bacterial chromosomal origin, oriC, and at the origins of many plasmids. The concentration of DnaA protein is an important factor in determining when initiation occurs during the cell cycle. Methylation of GATC sites in the dnaAp2 promoter, two of which are in the -35 and -10 sequences, has been predicted to play an important role in regulating dnaA gene expression during the cell cycle because the promoter is sequestered from methylation immediately following replication. Mutations that eliminate these two GATC sites but do not substantially change the activity of the promoter were introduced into a reporter gene fusion and into the chromosome. The chromosomal mutants are able to initiate DNA replication synchronously at both moderately slow and fast growth rates, demonstrating that GATC methylation at these two sites is not directly involved in providing the necessary amount of DnaA for precise timing of initiation during the cell cycle. Either sequestration does not involve these GATC sites, or cell cycle control of DnaA expression is not required to supply the concentration necessary for correct timing of initiation.

Bacterial Proteins↗
PubMed1999

NTS catecholamine cell recruitment by hemorrhage and hypoxia.

Immunolabelling for Fos and tyrosine hydroxylase was used to determine the patterns of activation of nucleus tractus solitarius catecholamine cells in response to graded levels of hemorrhage (0, 4, 8, 12 and 16 ml/kg) and systemic hypoxia (21, 14, 12, 10 and 8% O2) in conscious rats. Both stimuli elicited graded catecholamine cell recruitment with thresholds of 8 ml/kg and 12% O2. The majority of responsive neurons were A2 noradrenergic rather than C2 adrenergic cells. After hemorrhage most Fos-positive catecholamine cells were found below obex whereas most hypoxia-responsive cells were rostral to obex. These distinctive patterns of catecholamine cell recruitment may explain the differences in neuroendocrine responses to these stimuli.

Animals↗
PubMed1999

The substance P antagonist L-760,735 inhibits stress-induced NK(1) receptor internalisation in the basolateral amygdala.

The distribution of NK(1) receptor immunoreactivity in the amygdaloid complex, induction of NK(1) receptor endocytosis in the amygdala following immobilisation stress, and the ability of pretreatment with the substance P antagonist L-760,735 or imipramine to block this response were examined in gerbils, a species with human-like NK(1) receptor pharmacology. Highest levels of immunolabelling were observed in the anterior, amygdalo-hippocampal and medial nuclei. Less dense labelling was observed in the basolateral nucleus, where it was possible to clearly visualise the distal dendrites of NK(1) immunoreactive neurones and quantify the effect of immobilisation stress on NK(1) receptor endocytosis morphology, a marker of local substance P release. Immobilisation for 1 h caused an approximately 60% increase in the number of dendritic processes undergoing NK(1) receptor endocytosis in the basolateral amygdala that was inhibited by acute pretreatment of animals with L-760,735 (3 mg/kg), but not by imipramine (10 mg/kg). These findings are consistent with other evidence that the amygdala represents a possible site of action for the antidepressant and anxiolytic efficacy of substance P antagonists.

Amygdala↗
PubMed1999

Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis.

Since the Chlamydia pneumoniae (C. pneumoniae)-specific antibody was shown to be associated with acute myocardial infarction and chronic coronary heart disease, the role of C. pneumoniae in the etiology of cardiovascular disease has been studied by a number of groups. We investigated the association between the C. pneumoniae-specific antibody, measured by microimmunofluorescence, risk factors for cardiovascular disease, and atherosclerosis in a randomly selected urban population. Overall, immunoglobulin-G (IgG) seroprevalence to C. pneumoniae in this sample of 1,034 subjects was 58%, whereas IgA seroprevalence was 32%. There was a decline in seropositivity with age for IgG but not IgA. Men were more likely than women to be IgG (66% vs 51%, chi-square p = 0.001) and IgA seropositive (36% vs 28%, chi-square p = 0.005). Current smokers had higher IgA seropositivity than nonsmokers (43% vs 30%). Those patients with a family history of cerebrovascular disease were more likely to have IgG antibody than those without (75% vs 57%, chi-square p= 0.007). Neither IgG nor IgA seropositivity was associated with the standard risk factors of hypertension, hyperlipidemia, or family history of ischemic heart disease, nor was seropositivity associated with carotid intima medial thickening (IMT) or atherosclerotic plaque as measured by carotid B-mode ultrasound. There was no difference between those participants who were IgG or IgA seropositive and seronegative in measurements of mean IMT, prevalence of abnormal IMT, and percentage with atherosclerotic plaque. In conclusion, although C. pneumoniae was associated with several risk factors for cardiovascular disease in a large cross-sectional population, we found no independent association between seroprevalence to C. pneumoniae and carotid atherosclerosis as measured by carotid IMT.

Adult↗
PubMed1999

Regional anesthesia. Nerve blocks of the extremities and face.

Regional nerve blocks are useful for anesthetizing the hand and fingers, the foot and toes, and the face and mouth. These simple procedures may be performed prior to wound repair or surgery of the affected area. The authors discuss the indications, techniques, dosages, and potential complications of regional anesthesia.

Ankle↗
PubMed1999

theta, a novel gamma-aminobutyric acid type A receptor subunit.

gamma-Aminobutyric acid type A (GABA-A) receptors are a major mediator of inhibitory neurotransmission in the mammalian central nervous system, and the site of action of a number of clinically important drugs. These receptors exist as a family of subtypes with distinct temporal and spatial patterns of expression and distinct properties that presumably underlie a precise role for each subtype. The newest member of this gene family is the theta subunit. The deduced polypeptide sequence is 627 amino acids long and has highest sequence identity (50.5%) with the beta1 subunit. Within the rat striatum, this subunit coassembles with alpha2, beta1, and gamma1, suggesting that gamma-aminobutyric acid type A receptors consisting of arrangements other than alpha beta + gamma, delta, or epsilon do exist. Expression of alpha2beta1gamma1theta in transfected mammalian cells leads to the formation of receptors with a 4-fold decrease in the affinity for gamma-aminobutyric acid compared with alpha2beta1gamma1. This subunit has a unique distribution, with studies so far suggesting significant expression within monoaminergic neurons of both human and monkey brain.

Amino Acid Sequence↗
PubMed1999

Differential recruitment of hypothalamic neuroendocrine and ventrolateral medulla catecholamine cells by non-hypotensive and hypotensive hemorrhages.

We performed c-fos expression experiments in conscious rats to quantify the threshold and extent of activation of hypothalamic neuroendocrine cells in response to non-hypotensive and hypotensive hemorrhages allowing us to assess whether their pattern of recruitment corresponded to known oxytocin, vasopressin and ACTH release patterns. Also, because previous studies have implicated ventrolateral medulla catecholamine cells in the generation of certain hypothalamic neuroendocrine cell responses, we examined the response of ventrolateral medulla catecholamine cells to non-hypotensive and hypotensive hemorrhages and directly tested their role in regulating neuroendocrine cell responses to hypotensive hemorrhage. Animals were subjected to hemorrhages of 0, 4, 8, 12 or 16 ml/kg BW, the latter two levels being hypotensive. We found that only supraoptic nucleus vasopressin cells were significantly activated by the smallest non-hypotensive hemorrhage (4 ml/kg), which corresponds to reports that only vasopressin is released into the plasma after a small hemorrhage. Hypotensive hemorrhages resulted in significant recruitment of paraventricular and supraoptic oxytocin and vasopressin cells and parvocellular cells of the medial division of the paraventricular nucleus. Vasopressin cells were recruited in much greater numbers than oxytocin cells, which is in agreement with previous findings that there is a greater release of vasopressin than oxytocin into the plasma after hypotensive hemorrhage. In addition, medial parvocellular cells of the paraventricular nucleus, most likely to be tuberoinfundibular-projecting corticotropin-releasing factor cells, were activated by hypotensive hemorrhage only when arterial pressure dropped below 60 mmHg which also corresponds well with the plasma release response of ACTH. Ventrolateral medulla catecholamine cells were only recruited by hypotensive hemorrhages. While caution must be exercised in interpreting an absence of response, this certainly suggests that catecholamine cells are unlikely to have a role in the activation of supraoptic neurosecretory cells in response to non-hypotensive hemorrhages. Unilateral lesions of the ventrolateral medulla catecholamine cell column, corresponding primarily to the location of A1 noradrenergic cells, significantly reduced the hypotensive hemorrhage-induced activation of hypothalamic vasopressin, oxytocin and medial parvocellular paraventricular nucleus cells. This suggests that A1 noradrenergic cells contribute to the activation of these neuroendocrine cell populations, including oxytocin cells, which is an unexpected finding. More significantly, however, because the reduction in responsiveness after A1 lesions was similar for all cell categories, it seems likely that other factors must determine the differential recruitment of hypothalamic neuroendocrine cells in response to a hypotensive hemorrhage.

Animals↗