Search PubMed⌕ Search

Biomedical subjects

J D Smith

Publications and source records attributed to J D Smith.

At least 199 records · Page 11Linked to original sources
PubMed1992

Multistate outbreak of hepatitis A associated with frozen strawberries.

A multistate outbreak of hepatitis A was traced to frozen strawberries processed at a single plant. Among 827 students and 60 teachers at an elementary school in Georgia during a 2-week period, 15 developed hepatitis A. Three months later, among 174 residents and 467 staff in an institution for the developmentally disabled in Montana during a 3-week period, 13 developed hepatitis A. Primary attack rates were 10% in the school and 8% in the institution. Cohort analysis in the school implicated consumption of strawberry shortcake in hepatitis A virus (HAV) infection (relative risk, 7.6; 95% confidence interval, 1.04-55.6). In the institution, such analysis implicated desserts and uncooked strawberries as the most biologically plausible vehicle of HAV transmission. Molecular analysis of HAV from patients in the two outbreaks revealed that the viral genomes were genetically identical and distinct from other known US strains. Contamination of food products before retail distribution is rare but should be considered in investigating common-source outbreaks of hepatitis A.

Adult↗
PubMed1992

Specificity of lymphocytotoxic antibodies formed after cardiac transplantation and correlation with rejection episodes.

Eighty-two patients have been studied to determine the class and specificity of lymphocytotoxic antibodies produced during the 6 months following cardiac transplantation. Weekly serum samples were monitored for panel-reactive lymphocytotoxic antibodies (PRA) and donor reactive lymphocytotoxic antibodies using dithiothreitol to determine immunoglobulin class. Sera containing donor-reactive antibodies were further analyzed in a cytotoxic inhibition assay to determine whether the antibodies were directed against HLA or non-HLA determinants. A total of 67 (82%) of the patients produced detectable PRA following transplantation, no correlation was found between PRA and the incidence and severity of rejection. In 33 cases where an HLA specificity was defined, the antibody was not directed against the donor HLA phenotype. In contrast, the 32 (53%) recipients who had formed donor-reactive antibodies within 6 months of operation had required significantly more antirejection therapy (methylprednisolone) than the crossmatch-negative recipients (P less than 0.01). This was the case for both IgG and IgM responses. Of 24 positive donor responses, 18 were found to be specific for HLA antigens. These were both IgM (6 cases) and IgG (12 cases) HLA-specific antibodies, and their occurrence was strongly correlated with rejection (P less than 0.001).

Adult↗
PubMed1992

Polymorphism in the human apolipoprotein A-I gene promoter region. Association of the minor allele with decreased production rate in vivo and promoter activity in vitro.

We investigated a common polymorphism in the human apolipoprotein A-I gene promoter at a position 76 bp upstream of the transcriptional start site. 54 human subjects, whose apoAI production rates had been determined by apoAI turnover studies, were genotyped at this polymorphic position by a novel technique using polymerase chain reaction followed by primer extension. 35 subjects were homozygous for a guanosine (G) at this locus and 19 were heterozygous with a guanosine and adenosine (A). The apoAI production rates were significantly lower (by 11%) in the G/A heterozygotes than in the G homozygotes (P = 0.025). In spite of the apparent effect of this apoAI gene promoter polymorphism on the apoAI production rate, there was no effect on HDL cholesterol or apoAI levels. To investigate whether the observed difference in apoAI production rates was related to differential gene expression of the two alleles, promoters containing either allele were linked to the reporter gene chloramphenicol acetyltransferase, and relative promoter efficiencies were determined after transfection into the human HepG2 hepatoma cell line. The A allele expressed only 68% +/- 5% as well as the G allele, a result consistent with the in vivo apoAI production rate data.

Alleles↗
PubMed1992

Feeding studies in rats with mineral hydrocarbon food grade white oils.

This investigation compared the effects of feeding rats diets containing food grade white oil processed by either conventional oleum treatment or the more modern method of catalytic hydrogenation. In two separate experiments, male or female Fischer-344 rats were given free access for 90 days to diets containing 0, 10, 100, 500, 5,000, 10,000, or 20,000 ppm of either oleum-treated white oil (OTWO) or hydrotreated white oil (HTWO). There were no mortalities and no adverse clinical signs associated with feeding either white oil. Treatment-related effects evidenced by hematological, clinical chemical, and pathological changes were generally dose-related and more marked in female than in male rats, and the OTWO caused a greater pathological response than the HTWO. Tissue residues of saturated hydrocarbons were up to 5.2 times higher in female rats than in males. Rats fed 5,000 ppm or more of either white oil showed dose-related alterations in several hematological and clinical chemistry variates associated mainly with hepatic damage or functional alteration. At necropsy, mesenteric lymph nodes were enlarged, and increases in weight of liver, kidney, and spleen were significant. Microscopic changes were characterized by multifocal lipogranulomata in mesenteric lymph node and liver. No changes were observed in rats fed OTWO or HTWO for 90 days at dietary concentrations of 10 or 100 ppm, equivalent to a minimum intake of 0.65 and 6.4 mg/kg/day, respectively. Differences in degree of pathological response associated with each oil may have been due to their differences in specification rather than processing method.

Animals↗
PubMed1992

A canine model for studying laryngospasm and its prevention.

Laryngospasm, if prolonged, can result in serious sequelae due to the lack of a uniformly effective treatment. Prevention, therefore, through pharmacologic intervention, is an attractive concept. In order to study the effects of various drugs in preventing laryngospasm, a reliable animal model capable of producing sequential, repetitive episodes of laryngospasm is necessary. In this study, the canine model of laryngospasm previously described by Aviv, et al. was modified to overcome technical factors which limited its use in this regard. Details of the technique and the results from eight animals will be presented. Results in two animals with the use of prophylactic topical lidocaine will also be discussed. The reliability and reproducibility of this model make it ideal for the study of laryngospasm and open the way for investigation into its prevention.

Administration, Topical↗
PubMed1992

Sonography of the bladder after ureteral reimplantation.

Pre- and postoperative sonograms were reviewed in 59 children who underwent ureteral reimplantation to assess the frequency, location, extent, and evolution over time of focal thickening of the posterior bladder wall and bladder base after reimplantation. The interval between reimplantation and follow-up sonography ranged from 2 weeks to 12.36 years (mean, 1.29 years). Thirty-two patients (54.2%) had focal thickening of the posterior bladder wall and trigone after reimplantation. The earlier after reimplantation the children were first evaluated with sonography, the much more frequently was thickening observed. Thirteen had fusiform thickening along the submucosal tunnel and twenty-four had a hyperechoic nodule at the trigone. The thickening resolved in one third of the children and is presumed to have represented postoperative edema in these cases. However, on the sonographic appearance alone it was not possible to differentiate transient changes resulting from postoperative edema from those representing developing fibrosis or granuloma formation.

Adolescent↗
PubMed1992

Kynurenic acid analogues with improved affinity and selectivity for the glycine site on the N-methyl-D-aspartate receptor from rat brain.

The glycine site on the N-methyl-D-aspartate (NMDA) subtype of receptors for the excitatory neurotransmitter glutamate is a potential target for the development of neuroprotective drugs. We report here two chemical series of glycine site antagonists derived from kynurenic acid (KYNA), with greatly improved potency and selectivity. Disubstitution with chlorine or bromine in the 5- and 7-positions of KYNA increased affinity for [3H]glycine binding sites in rat cortex/hippocampus P2 membranes, with a parallel increase of potency for antagonism of NMDA-evoked responses in the rat cortical wedge preparation. The optimal compound was 5-I,7-Cl-KYNA, with an IC50 for [3H]glycine binding of 29 nM and an apparent Kb in the cortical wedge preparation of 0.41 microM. Reduction of the right-hand ring of 5,7-diCl-KYNA reduced affinity by 10-fold, but this was restored by substitution in the 4-position with the trans-phenylamide and further improved in the trans-benzylamide. The optimal compound was the transphenylurea (L-689,560), with an IC50 of 7.4 nM and an apparent Kb of 0.13 microM. Both series of compounds displayed a high degree of selectivity for the glycine site, having IC50 values of greater than 10 microM versus radioligand binding to the glutamate recognition sites of NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate receptors and the strychnine-sensitive glycine receptor. Selectivity versus AMPA receptor-mediated responses was also apparent in the rat cortical wedge and in patch-clamp recordings of cortical neurons in culture. Experiments using [3H]dizocilpine (MK-801) binding indicated that 5,7-diBr-KYNA, 5,7-diCl-KYNA, 5-I,7-Cl-KYNA, and L-689,560 all behaved as full antagonists and were competitive with glycine. Patch-clamp recordings of cortical neurons in culture also indicated that NMDA-induced currents were antagonized by competition for the glycine site, and gave no evidence for partial agonist activity. pKi values for 5,7-diBr-KYNA and L-689,560 in these experiments were 7.2 and 7.98, respectively, similar to the affinities of these compounds in the glycine binding assay. The high affinity and selectivity of these new derivatives make them useful tools to investigate the function of the glycine site on the NMDA receptor.

Animals↗
PubMed1991

Cerebral-blood-flow-velocity measurements in neonates: technique and interobserver reliability.

The interobserver reliability for absolute cerebral-blood-flow-velocity measurements by colour and duplex Doppler sonography was tested in 32 neonates with a mean birth weight of 1489 (SD 644) g, and a gestational age of 29.9 (SD 3.5) weeks. Using standardized technique, two observers recorded on videotape, the Doppler spectrum of the anterior cerebral artery, the intracranial internal carotid artery and the middle cerebral artery. Peak systolic flow, end diastolic flow, mean flow velocity, resistive index and pulsatility index were computed from 3 consecutive waveforms by each observer. The estimates of interobserver reliability using the intraclass correlation coefficient of the examiners varied from 0.95 to 1.00. Therefore, cerebral blood flow velocity can be reliably measured in premature infants.

Blood Flow Velocity↗
PubMed1991

Effect of movement and position on muscle activity in tension headache sufferers during and between headaches.

This paper presents the results of two studies. In the first, 20 tension headache subjects were evaluated in both a headache and non-headache state on bilateral trapezius and unilateral frontalis electromyographic activity during six positions: standing, bending from the waist, rising, sitting with back unsupported, sitting with back supported, and prone. Results indicated no effect of headache state on either measure. In a second study, 11 of the tension headache sufferers in Study One and 11 age-matched controls were compared on the same measures (controls were assessed two times, with a one-week duration separating evaluations). Results indicated a diagnosis by position interaction, with post-hoc tests revealing the muscle activity of tension headache sufferers to be considerably higher during the prone position than that of non-headache controls. Non-significant trends were found when examining the data for clinically significant abnormalities (90% of the headache sufferers were found to have significant clinical abnormalities).

Adult↗
PubMed1991

Identification and exploitation of the sigma-opiate pharmacophore.

Certain benzomorphan "sigma-opiates" such as N-allylnormetazocine (NANM) bind at sigma receptors with modest affinity and with little selectivity (i.e., they also bind at phencyclidine or PCP sites). In order to identify the primary pharmacophore of the benzomorphans, we prepared several amine-substituted derivatives of 1-phenyl-2-aminopropane. Several simple alkyl-substituted analogues were shown to bind at sigma sites with affinities comparable to that of NANM itself; among these was the N-benzyl derivative 9 (Ki = 117 nM). Lengthening the spacer between the terminal amine and the phenyl group from one to five methylene units resulted in a significant increase in affinity (e.g. 15, Ki = 6.3 nM). In addition, unlike the benzomorphans, these phenalkylamines do not bind at PCP sites. The results of the present study reveal that (a) the 1-phenyl-2-aminopropane nucleus of the benzomorphans is sufficient for binding at sigma sites provided that the terminal amine is not a primary amine and that (b) introduction of (phenylalkyl)amine substituents affords compounds that represent a new class of high-affinity sigma-selective agents.

Animals↗
PubMed1991

Binding of substituted and conformationally restricted derivatives of N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane at sigma-receptors.

Certain benzomorphans, such as N-allylnormetazocine, are classical "sigma-opiates" that bind both at sigma and phencyclidine (PCP) binding sites with modest affinity. Recently, we identified N-substituted 2-phenylaminoethane as being the primary sigma-pharmacophore of the benzomorphans and demonstrated that 1-phenyl-2-aminopropane (2) derivatives, depending upon their terminal amine substituents, constitute a novel class of high-affinity sigma-selective agents. With this pharmacophore, it is shown in the present investigation that the aromatic hydroxyl group (a prime feature of all the sigma-opiates) contributes little to the binding of 2 at sigma-sites. It is also demonstrated that an N-substituted aminotetralin moiety (such as 17, a conformationally restricted analogue of 2) may also be considered a sigma-opiate pharmacophore. Unlike the sigma-opiates, derivatives of 2 and 17 display no affinity for PCP sites and must consequently lack those structural features important for the binding of benzomorphans at PCP sites. Because 3-phenylpiperidines and related sigma-ligands also possess a phenylalkylamine imbedded within their structures, we propose that the 2-phenylaminoethane moiety is a common sigma-pharmacophore for derivatives of 2, the 3-phenylpiperidines, and the sigma-opiates.

Animals↗
PubMed1991

Treatment outcomes of impaired physicians in Oklahoma.

Data on one hundred twenty impaired physicians were analyzed to determine treatment outcomes from three differing types of chemical dependency treatment. The data showed that long-term (three to four months) treatment geared specifically to health care professionals was the most effective treatment modality, showing higher rates of favorable treatment outcomes measured by abstinence from alcohol and other drugs.

Combined Modality Therapy↗
PubMed1990

Effect of the methylation inhibitors 3-deazaadenosine and 3-deazaaristeromycin on phosphatidylcholine formation in Tetrahymena.

The methylation inhibitors 3-deazaadenosine and 3-deazaaristeromycin inhibited the methylation pathway for phosphatidylcholine formation in Tetrahymena. At the same time, the phosphatidylcholine levels within the cell were maintained by increased use of the phosphotransferase pathway. Cell growth was not affected at inhibitor concentrations up to 50 microM but was 50% inhibited at inhibitor concentrations of 100 microM. This growth inhibition was not reversed by the addition of choline to the growth medium. The added choline resulted in greater use of the phosphotransferase pathway, even in uninhibited cultures, but there was no effect on phosphatidylcholine levels, pointing to a much tighter control on phosphatidylcholine formation than exists in animal cells.

Adenosine↗
PubMed1990

Accumulation of human apolipoprotein E in the plasma of transgenic mice.

Three separate lines of transgenic mice were created with integrated copies of an 11.1-kilobase pair human DNA fragment containing the apolipoprotein (apo) E gene. The endogenous mouse apoE gene is primarily expressed in the liver with varying levels of expression in other tissues. However, in all three transgenic lines high levels of human apoE mRNA were detected only in the kidney, with lower levels found in the liver and other tissues; despite this profile of human apoE mRNA, human apoE was found in the plasma of the transgenic mice at levels comparable to those found in human plasma. All of the human apoE in the plasma of the transgenic mice was associated with lipoproteins. These results suggest that the domain responsible for the high level of apoE expression in liver lies outside of the microinjected DNA fragment and that an ectopic site of expression of an introduced gene may be permissive for the accumulation of its protein in plasma.

Animals↗