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Biomedical subjects

D L Smith

Publications and source records attributed to D L Smith.

At least 181 records · Page 10Linked to original sources
PubMed1995

DNA bending by the a1 and alpha 2 homeodomain proteins from yeast.

Structural and biochemical studies of monomer homeodomain-DNA complexes have not so far revealed any cases of pronounced DNA distortion. In this paper we show that multimeric complexes of the yeast homeodomain proteins a1 and alpha 2 induced significant bends in their operators upon binding. Based on a series of circular permutation experiments, we found that a dimer of alpha 2 bound to operator DNA produced a mild bend in the DNA, whereas the alpha 2-MCM1-DNA and the a1-alpha 2-DNA complexes exhibited much sharper bends. As these latter two complexes represent the in vivo form of DNA-bound a1 and alpha 2, we conclude that, in the cell, these homeodomain proteins are associated with pronounced bends in DNA. We discuss possible roles for these bends in transcriptional repression.

Base Sequence↗
PubMed1995

Opioid effects on spinal [3H]5-hydroxytryptamine release are not related to their antinociceptive action.

Several opioid compounds were evaluated for an ability to modulate the K(+)-stimulated release of [3H]serotonin ([3H]5-hydroxytryptamine, [3H]5-HT) from rat spinal cord synaptosomal and tissue slice preparations. Selective kappa-opioid receptor agonists depressed K(+)-stimulated release of the radiolabelled transmitter from both tissue preparations, an effect which was reversed by norbinaltorphimine. Conversely, the selective mu- and delta-opioid receptor agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO) and [D-Pen2,D-Pen5]enkephalin (DPDPE), respectively, enhanced the K(+)-stimulated release of [3H]5-HT. This effect was only seen using the tissue slice preparation. When used at concentrations near its reported Kd for mu-opioid receptors, the selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) blocked the action of DAMGO, but had no effect on the action of DPDPE. However, higher concentrations of CTOP, as well as all effective concentrations of selective delta-opioid receptor antagonists, blocked the action of both DAMGO and DPDPE. All agonist effects on spinal 5-HT release, regardless of the tissue preparation, were only seen at high (microM) concentrations. Moreover, effects of the opioid agonists were not consistent with the reported involvement of spinal 5-HT neurotransmission in the mediation of their antinociceptive action. Thus, the ability of opioids to modulate spinal 5-HT release appears to be of minimal physiological significance.

Amino Acid Sequence↗
PubMed1995

Glutathione adducts, not carbamylated lysines, are the major modification of lens alpha-crystallins from renal failure patients.

alpha-Crystallins from the water-soluble and the water-insoluble, guanidine-soluble portions of lenses from four renal failure patients and two normal donors of similar age were isolated and enzymatically digested into peptides. Molecular weights of the peptides, determined by fast atom bombardment mass spectrometry, indicated modifications specifically associated with renal failure. The only modifications observed in the alpha-crystallins from renal failure patients, but not in the normal old lenses, were glutathione adducts to Cys 131 and Cys 142. These adducts were present in the lenses of all four renal failure patients, but not in the two normal old lenses. The four lenses from the renal failure patients were searched for evidence of carbamylation at lysyl or cysteinyl residues: carbamylation was not detected. Because the same mass spectrometric methods had previously demonstrated sufficient sensitivity and specificity to detect as little as 5% modification in the examination of in vitro carbamylated bovine lenses, these results indicated that carbamylation is not a major modification of the lens alpha-crystallins of renal failure patients.

Aged↗
PubMed1995

Netherton's syndrome: a syndrome of elevated IgE and characteristic skin and hair findings.

Netherton's syndrome is a rare symptom complex characterized by greatly elevated IgE levels with atopic manifestations, an ichthyotic skin disorder (ichthyosis linearis circumflexa and/or congenital lamellar ichthyosis), and the characteristic hair abnormality trichorrhexis invaginata. It may be confused with atopic dermatitis but does not respond to topical corticosteroid treatment. Netherton's syndrome is therefore of considerable importance to allergists. In this article we report the results of the clinical and immunologic evaluation of a previously unreported patient who responded to treatment with 12% ammonium lactate lotion and management of his allergic disease. Furthermore, we have reviewed the English literature and compared the findings in our patient with those of 43 other reported patients. Our patient shared the features of other previously reported patients with this disorder. We conclude that this disease should be included among the other disorders with elevated IgE. Patients may benefit from evaluation and treatment of their allergic symptoms and topical skin treatment with ammonium lactate.

Biopsy, Needle↗
PubMed1995

Differences in calcium metabolism between adolescent and adult females.

A 3-wk metabolic study measured calcium balance in 14 white adolescent girls and 11 young adult women. Subjects were housed in a sorority to simulate a free-living environment. A 6-d menu cycle consisted of foods typically eaten by teenagers and averaged 1332 mg Ca/d. Adolescents had a significantly higher calcium balance of 326 +/- 107 mg/d (mean +/- SD) than adults, who averaged 73 +/- 104 mg/d (P < 0.001). No adult > age 21 y was in positive calcium balance. Adolescents had lower urinary calcium excretion values (P < 0.001), lower fecal calcium excretion (P < 0.01), and greater net absorption (P < 0.001) than adults. Calcium balance was negatively correlated with years postmenarche (r = -0.788, P = 0.0001) and height (r = -0.650, P = 0.001). Net calcium absorption was positively correlated with parathyroid hormone concentrations (r = 0.537, P = < 0.01). Thus, the growth demands of adolescents are met by more efficient net absorption and retention of calcium compared with young adults.

Adolescent↗
PubMed1995

LRP1, a gene expressed in lateral and adventitious root primordia of arabidopsis.

We describe a gene that is expressed in lateral and adventitious root primordia of Arabidopsis. The gene was identified by expression of a transposon-borne promoterless beta-glucuronidase gene in lateral root primordia. The gene, designated LRP1 for lateral root primordium 1, and its corresponding cDNA were cloned and sequenced. The expression pattern of the gene in lateral root primordia was confirmed by in situ hybridization with LRP1 cDNA probes. The LRP1 gene encodes a novel protein. LRP1 expression is activated during the early stages of root primordium development and is turned off prior to the emergence of lateral roots from the parent root. Insertion of the transposon in the LRP1 gene disrupted its expression. To evaluate the homozygous insertion line for a mutant phenotype, several aspects of wild-type lateral root development were analyzed. A mutant phenotype has not yet been identified in the insertion line; however, there is evidence that the gene belongs to a small gene family. LRP1 provides a molecular marker to study the early stages of lateral and adventitious root primordium development.

Amino Acid Sequence↗
PubMed1995

Outcome of pregnancy in women with cystic fibrosis.

BACKGROUND: As women with cystic fibrosis are living longer, pregnancy is becoming increasingly common. The combined experience of pregnancies in women with cystic fibrosis from adult centres in the Midlands and North of England has been examined. METHODS: A retrospective study of the case notes of 22 pregnancies in 20 patients with cystic fibrosis examined changes in lung function, body weight, and microbiological status during the course of pregnancy. Duration of pregnancy, birth weight, and maternal survival were amongst other variables studied. The relation between values before pregnancy and important outcome measures were examined. RESULTS: Eighteen of 22 pregnancies were completed producing healthy, non-cystic fibrosis infants (12 female). Mothers lost 13% of FEV1 and 11% of FVC during pregnancy, most of which was regained. Body weight changes were variable, but most mothers gained weight (mean weight gain 5.7 kg). Microbiological status remained unchanged. Six infants were preterm and two were light for dates. Four mothers died up to 3.2 years following delivery. Of the prepregnancy parameters examined, %FEV1 showed the best correlation with maternal weight gain, gestation, birth weight, and maternal survival. CONCLUSIONS: Pregnancy was well tolerated by most mothers with cystic fibrosis although those with moderate to severe lung disease (%FEV1 < 60%) before pregnancy fared worse, producing preterm infants and suffering increased loss of lung function and mortality compared with mildly affected mothers. Prepregnancy %FEV1 appears to be the most useful predictor of important outcome measures in pregnancies in women with cystic fibrosis.

Adolescent↗
PubMed1995

Human renin 5'-flanking DNA to nucleotide-2750.

Renin is one of the most important factors in blood pressure and electrolyte regulation in mammals and the renin locus has been implicated in hypertension. To assist studies of promoter control we therefore determined the 5'-flanking sequence of the human gene (REN) to residue -2750 relative to the transcription start site (+1). Sites of homology to consensus sequences for binding of trans-acting factors involved in transcriptional control of other genes were identified, and functionality for two of these (a CRE and Pit-1 site) have so far been demonstrated.

Base Sequence↗
PubMed1995

Strategic implications of a "paperless" information system.

The movement of the typical medical practice toward increased size, dispersed operations and formalized affiliations with hospitals, insurance companies and other providers has exacerbated the problems of information management. Antiquated information systems have become a serious impediment to efficient operations in many medical practices. This professional paper describes the advantages, obstacles and necessity of implementing a comprehensive electronic information system.

Electronic Data Processing↗
PubMed1995

Second opinion: a computer expert system designed to aid in the determination of spectacle lens prescriptions.

BACKGROUND: Expert systems (ESs) are computer programs that simulate the decision-making ability of human experts. In this project, an ES was developed that used optometric data and decision rules to determine spectacle lens prescription powers. METHODS: Decision rules derived from clinical experience and standard references were provided to a commercially available shell program to create an ES called Second Opinion. The ES determined spherical, cylindrical, and add powers designed to provide maximum acuity consistent with a high probability of patient acceptance. CONCLUSIONS: Second Opinion demonstrates how a computer program can be used to analyze optometric data and offer suggestions regarding lens prescriptions.

Adult↗
PubMed1995

Biologic potency and immunoblotting studies of extracts of three cockroach species.

BACKGROUND: Although cockroaches are responsible for severe allergic disease, cockroach extracts are not yet standardized by the ID50EAL method, nor have the allergens been completely characterized. OBJECTIVE: To determine biologic potency and immunoblotting patterns of whole-body extracts of three cockroach species: Periplaneta americana, Blattella germanica, and Blatta orientalis. METHOD: Twenty-four subjects puncture test positive to mixed cockroach extract were puncture tested with the three extracts. Fourteen qualified for endpoint titration testing by the ID50EAL method to P. americana with a sum of erythema (sigma E) > or = 20 mm by puncture testing, while 13 qualified for B. germanica and 12 qualified for B. orientalis. RESULTS: The mean D50s were 9.67 +/- 1.33 (mean +/- SD) for P. americana, 10.24 +/- 1.16 for B. germanica, and 10.36 +/- 1.40 for B. orientalis, resulting in a potency of 1000 BAU/mL for each extract. Omitting data from subjects with puncture sigma E < 30 mm did not change the calculated potency. Sixteen serum specimens revealed up to 17 bands with molecular weight 14 to 263 kD by SDS-PAGE immunoblotting. Four specimens showed no bands; of these, one had a positive RAST only to P. americana and one only to B. germanica. There was no correlation between number of bands or RAST counts with D50. CONCLUSIONS: IgE immunoblots of cockroach-allergic patients vary considerably as to the number and intensity of bands. Most patients react similarly to all three species. Current nonstandardized products (1:10 wt/vol) in glycero-Coca's solution appear to contain approximately 1000 BAU/mL. Ideally these extracts should be more potent, eg, 10,000 BAU/mL.

Adult↗
PubMed1995

Prospective analysis of outcome after cardiopulmonary resuscitation in critically ill surgical patients.

BACKGROUND: This study was done to examine the outcome of cardiopulmonary resuscitation (CPR) in the surgical intensive care unit (SICU) and to identify factors preceding cardiopulmonary arrest that could predict survival. STUDY DESIGN: We prospectively collected demographic, laboratory, diagnostic, and complications data in our SICU database on 5,237 consecutive patients and reviewed the charts of all patients receiving CPR. RESULTS: Cardiopulmonary resuscitation was performed upon 1.1 percent (55 of 5,237 patients) of patients in the SICU. Twenty-nine percent (16 of 55 patients) survived greater than 24 hours but died in the hospital, and 13 percent (seven of 55 patients) survived to discharge. No patient with a worsening Glasgow Coma Scale (GCS) score, acute physiology score (APS), or any acute organ failure who had cardiopulmonary arrest survived. Survival after CPR for patients with a stable or improving APS was 32 percent (p < 0.01). CONCLUSIONS: Patients in the SICU who survived CPR had a stable or improving clinical course as determined by APS and GCS score, and had not had acute organ failure. Patients who were critically ill with a declining clinical course did not survive after CPR.

APACHE↗
PubMed1995

Spinal nonadrenergic imidazoline receptors do not mediate the antinociceptive action of intrathecal clonidine in the rat.

The intrathecal administration of clonidine to rats results in profound antinociception which is thought to be mediated through an interaction of the agonist with spinal alpha-2 adrenergic receptors. However, clonidine has been shown to also interact with nonadrenergic imidazoline receptors. Consequently, this study was undertaken to determine if nonadrenergic imidazoline receptors are present in the rat spinal cord, and the extent to which they are involved in the antinociceptive action of spinally administered clonidine. By using the tail-flick test, the antinociceptive action of spinally administered clonidine was found to be blocked completely by the intrathecal administration of the imidazoline idazoxan. Similarly, yohimbine (a nonimidazoline alpha-2 adrenergic antagonist) also blocked completely the antinociceptive action of clonidine. Results of radioligand binding studies demonstrated that norepinephrine did not interact with approximately 20% of all specific spinal sites labeled by 4 nM [3H]clonidine, indicating the presence of nonadrenergic spinal sites. Affinity data obtained from competition binding assays demonstrated that the spinal nonadrenergic sites labeled by [3H]clonidine possess little affinity for yohimbine. Therefore, nonadrenergic imidazoline receptors are not involved in the antinociceptive action of spinally administered clonidine.

Adrenergic alpha-Antagonists↗
PubMed1994

Proximal 2.6 kb of 5'-flanking DNA is insufficient for human renin promoter activity in renin-synthesizing chorio-decidual cells.

In order to determine the influence of proximal 5'-flanking DNA of the human renin gene (REN) in cells that express human renin, transient expression analyses were carried out in chorio-decidual cells. Constructs containing different lengths of REN promoter DNA, extending as far as 2595 bp upstream of the transcription start site, were unable to drive transcription of a chloramphenicol acetyl transferase reporter gene in chorio-decidual cells, nor in noncognate 293 or JEG-3 cells. The tk promoter was similarly inactive in constructs containing -2595 to -453 fragments of REN 5'-flanking DNA. In each cell type, the -2595 to -1300 DNA exerted a negative influence. Additional promoter- and cell type-dependent negative influences were noted for other regions of REN 5'-flanking DNA and the -453 to -145 DNA increased tk promoter activity 2.5-fold in chorio-decidual cells. By introducing the SV40 enhancer into constructs, a weak stimulation of the REN promoter was observed in chorio-decidual cells, but not in noncognate, JEG-3 cells, although the -2595 to -1300 DNA retained its negative influence in the cognate cell type. These results show that the proximal 2.6 kb of REN 5'-flanking DNA is unable to drive reporter gene activity in renin-synthesizing, chorio-decidual cells under basal conditions and suggest that trans-acting factors unique to at least this cell type, together with enhancer(s) located outside of the proximal 2.6 kb of REN promoter DNA tested, could be required for human renin promoter activity.

Chorion↗