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Biomedical subjects

T Nelson

Publications and source records attributed to T Nelson.

At least 37 records · Page 2Linked to original sources

Developmental time courses in the brain and kidney of two enzymes that oxidize gamma-hydroxybutyrate.

The postnatal developmental profiles of two enzymes that oxidize gamma-hydroxybutyrate (GHB) were examined during the period when the brain concentration of GHB was changing from the higher fetal level (7 microM) to the lower adult level (2 microM). At 20 days of age, the maximal oxidative capacity (Vmax) of GBH dehydrogenase (GHB-D) in the brain reached a rate that was approximately 50% greater than either adult or 18-day fetal values. The Vmax for GBH-oxoacid transhydrogenase (GHB-T) in the brain was negligible at 18 days of gestation but increased 40-fold by 20 days and 100-fold by 70 days after birth. In contrast to the brain, the GHB concentration in the kidney remained at approximately 65% of the adult level from birth to 15 days of age and then rose to adult levels. The activities of both GHB-D and GHB-T were 20% of their adult values in the newborn kidney, and both enzymes increased to near adult activities by 20 days. It appears that GHB-D is the predominant catabolic enzyme for GHB in the fetal and neonatal brain, whereas in the kidney both enzymes participate from the earliest time examined.

Alcohol Oxidoreductases

Regular use of a verbal pain scale improves the understanding of oncology inpatient pain intensity.

PURPOSE: This study was undertaken to determine if the daily use of a verbal pain scale could improve the correlation of pain perception between hospitalized oncology patients and their caregivers. PATIENTS AND METHODS: Hospitalized oncology patients were asked to rate verbally their average pain over the past 24 hours on a scale ranging from 0 to 10. The patients' primary-care physicians and nurses were asked the same question on the same morning after they had evaluated their patients. RESULTS: During a baseline study, only 64% of caregivers' pain scores were within two points of the respective patient's score. Caregivers tended to underestimate patients' pain scores. Caregivers were alerted to these poor results and then requested to ask each patient daily for the average pain score and record this score on the patient's medical record. Nonetheless, correlation between patients' and caregivers' pain scores remained poor (68% within two points of each other) during a second study. The major reason for the poor results appeared to be because caregivers did not routinely ask patients for pain scores. Subsequently, a renewed, more intensive educational effort was undertaken and a third study was conducted. During the third study, 85% of caregivers' and patients' pain scores were within two points of each other (P = .001 when compared with baseline). CONCLUSION: The enforced use of a simple verbal pain assessment tool appears to improve caregiver's understanding of the pain status of hospitalized oncology patients.

Caregivers

A ventilation-filtration unit for respiratory isolation.

OBJECTIVE: The development of a new method for achieving respiratory isolation in hospitals, clinics, and residential facilities, in response to the increasing risk of transmission of tuberculosis and the limitations of the currently available isolation systems. DESIGN: Ultraviolet (UV) light and ultra-low-penetration air filtration were combined with a ventilation unit and adapted for use in modular isolation rooms or for conversion of existing rooms. RESULTS: The ventilation-filtration unit efficiently cleared bacterial aerosols and particles > 0.2 microns from the air, maintained required negative pressures and airflows, and provided directional airflow within rooms.

Colony Count, Microbial

Patient choice: deciding between psychotropic medication and physical restraints in an emergency.

The legal requirement to use least restrictive interventions in emergency psychiatric treatment does not stipulate whether physical restraints or medication is least restrictive. There is no current consensus about how to determine least restrictive interventions in a generalizable manner. In this study patients who were clients in a public psychiatric emergency service were anonymously surveyed and asked to state their preferences for specific interventions in a psychiatric emergency. In a choice between physical restraints versus psychotropic medication, 64 percent of clients preferred medication; 36 percent preferred seclusion or restraint. The rank order of preferred modality was 1) benzodiazepines--31 percent, 2) neuroleptics--26 percent, 3) seclusion--24 percent, 4) restraints--10 percent. The rank order of last choice was different. Patients preference is an important factor in determining the appropriate intervention in an emergency. Patient participation offers an opportunity reconcile to clinical and legal objectives, to i improve compliance, and to enhance patient and staff safety.

Adult

Cell-specific accumulation of maize phosphoenolpyruvate carboxylase is correlated with demethylation at a specific site greater than 3 kb upstream of the gene.

Development of the C4 photosynthetic pathway relies upon the cell-specific accumulation of photosynthetic enzymes. Although the molecular basis of this cell-specific gene expression is not known, regulation appears to be exerted at the level of transcript accumulation. We have investigated the relationship between gene expression patterns and DNA methylation for genes of two of the C4 photosynthetic enzymes, ribulose bisphosphate carboxylase (RuBPCase) and phosphoenolpyruvate carboxylase (PEPCase). We found no correlation between methylation state and gene expression for either the large subunit or a small subunit gene of RuBPCase. In contrast, demethylation of a specific site 5' to the PEPCase gene was correlated with the light-induced, cell-specific accumulation of PEPCase mRNA. This differentially methylated site is positioned at great distance (greater than 3 kb) from the start of transcription. This observation is made more interesting by the fact that the immediate 5' region of the gene, and some of the coding region, represents an unmethylated CpG island. Such islands are normally associated with constitutively expressed genes.

DNA

An overview of gamma-hydroxybutyrate catabolism: the role of the cytosolic NADP(+)-dependent oxidoreductase EC 1.1.1.19 and of a mitochondrial hydroxyacid-oxoacid transhydrogenase in the initial, rate-limiting step in this pathway.

Two enzymes have been found which catalyze the initial step in the catabolism of GHB. The oxidation of GHB to SSA, catalyzed by both of these enzymes, is coupled to the reduction of an oxoacid. In the case of the mitochondrial transhydrogenase, the coupling is obligatory. Although coupling is not obligatory for the GHB dehydrogenase, the stimulation provided by the coupled reaction, and the nature of the kinetics of the uncoupled reaction, may not only allow the reaction to proceed, but may provide a means of regulating the rate of the reaction under in vivo conditions. Since the oxidation of GHB to SSA is the rate limiting step in the overall catabolic pathway (the rate of conversion of GHB to SSA proceeds at approximately one one thousandth of the rate at which SSA is oxidized to succinate by SSA dehydrogenase (30)), factors which regulate the rate of either or both of these enzymes will, in turn, influence tissue levels of endogenous GHB as well as the duration and magnitude of the physiological effect of a dose of GHB.

Alcohol Oxidoreductases

Spatial regulation of photosynthetic development in C4 plants.

Leaf development in C4 plants requires the morphological and functional differentiation of two photosynthetic cell types (bundle sheath and mesophyll). Photosynthetic reactions are split between bundle sheath and mesophyll cells, with each cell type accumulating a specific complement of photosynthetic enzymes. Current evidence suggests that in order to activate this cell-specific expression of photosynthetic genes, bundle sheath and mesophyll cells must interpret positional information distributed locally around each vein.

Carbon Dioxide

Modeling the dependence of hexose distribution volumes in brain on plasma glucose concentration: implications for estimation of the local 2-deoxyglucose lumped constant.

The steady-state distribution volumes of glucose, 3-O-methylglucose, and 2-deoxyglucose (2DG) are known to change as the concentration of glucose in plasma ranges from hypo- to hyperglycemic values. Model estimates of the three distribution volumes were compared with distribution volume values experimentally measured in the brains of conscious rats as the concentration of glucose in plasma was varied from 2 to 28 mM. The dependence on plasma glucose concentration of the 2DG lumped constant, the factor that relates the phosphorylation rate of 2DG to the net rate of glucose utilization at unit specific radioactivity in the plasma, had been determined previously in separate series of experiments. The model was extended to incorporate this dependence of the lumped constant. In the model both the transport and the phosphorylation barriers were assumed to be single and saturable. The values of their respective half-saturation concentrations and the ratio of the two maximum velocities for glucose were assumed to be invariant over the entire range of plasma glucose concentration. Good agreement between measured and estimated values for the distribution volumes and the lumped constant was attained over the full range of plasma glucose concentration. The model estimates reflected the progressive transport limitation of the brain glucose content as plasma glucose levels were reduced to hypoglycemic values. The results also indicated that these changes should be evident in the time course of 2DG in brain following administration by bolus or continuous infusion, and thus that indexes of local lumped constant change could be derived from the time course data.

3-O-Methylglucose

A quantitative approach to the characterization of cumulative and average solvent exposure in paint manufacturing plants.

Previous reports have attributed a range of neurobehavioral effects to low-level, occupational solvent exposure. These studies have generally been limited in their exposure assessments and have specifically lacked good estimates of exposure intensity. In the present study, the authors describe the development of two exposure variables that quantitatively integrate industrial hygiene sampling data with estimates of exposure duration--a cumulative exposure (CE) estimate and a lifetime weighted average exposure (LWAE) estimate. Detailed occupational histories were obtained from 187 workers at two paint manufacturing plants. Historic industrial hygiene sampling data for total hydrocarbons (a composite variable of the major neurotoxic solvents present) were grouped according to 20 uniform, temporally stable exposure zones, which had been defined during plant walk-through surveys. Sampling at the time of the study was used to characterize the few zones for which historic data were limited or unavailable. For each participant, the geometric mean total hydrocarbon level for each exposure zone worked in was multiplied by the duration of employment in that zone; the resulting products were summed over the working lifetime to create the CE variable. The CE variable was divided by the total duration of employment in solvent-exposed jobs to create the LWAE variable. The explanatory value of each participant's LWAE estimate in the regression of simple visual reaction time (a neurobehavioral test previously shown to be affected by chronic solvent exposure) on exposure was compared with that of several other exposure variables, including exposure duration and an exposure variable based on an ordinal ranking of the exposure zones.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Industry

IGF-I stimulates tropoelastin synthesis in neonatal rat pulmonary fibroblasts.

We have examined the effect of IGF-I on tropoelastin (TE) synthesis in cultured rat neonatal pulmonary fibroblasts, because this growth factor has been shown to stimulate TE synthesis in vascular smooth muscle cells. IGF-I stimulated TE and total protein synthesis in a dose-dependent manner even when cells were cultured in the medium supplemented with 0.5% FCS. The maximal stimulation was at IGF-I concentration 500 ng/mL and was an increase of 86 +/- 14 and 35 +/- 5% for TE and estimated total protein synthesis, respectively. There was a corresponding 95 +/- 20% increase in the TE mRNA/beta-actin mRNA ratio assessed by densitometry of the Northern blot analysis. At this low concentration of FCS, however, there was neither TE stimulation by dexamethasone alone nor in combination with IGF-I. We conclude that IGF-I stimulation of TE synthesis may occur in cells other than vascular smooth muscle cells and that there is no additive stimulation by glucocorticoids.

Animals

Report of the National Commission on Nurse Anesthesia Education. American Association of Nurse Anesthetists Medicare pass-through reimbursement for nurse anesthesia education programs.

Medicare pass-through dollars for paramedical education are one way hospitals can still get reimbursed on the basis of their costs under the prospective payment system. To qualify, a hospital must demonstrate that it has some involvement in the operation of the nurse anesthesia program. Establishment of a cost center for school-related expenses can help maximize reimbursement.

Accounting

Pyretic action of low doses of gamma-hydroxybutyrate in rats.

gamma-Hydroxybutyrate (GHB) has been found to have a biphasic effect on body temperature with increased body temperature after low doses (5-10 mg/kg) and decreased body temperature after high doses (300-500 mg/kg). Brain levels of GHB between 30 and 60 min post-injection of GHB were not altered by the low doses (5-10 mg/kg), although a dose of 200 mg/kg produced a large increase in the brain concentration.

Animals

Physical and acoustical properties of perfluorooctylbromide, an ultrasound contrast agent.

Perfluorooctylbromide (PFOB: C8F17Br) has been shown to be an effective ultrasound contrast agent when incorporated in tissues. The authors have recently demonstrated that PFOB also enhances tissues and Doppler signals during its capillary phase. To help elucidate the physical basis of their observations, the authors compared physical and acoustical properties of standard PFOB-lecithin emulsion with identical lecithin emulsion minus PFOB (vehicle) for concentrations of PFOB from 0% to 50% weight per volume. Propagation velocity, attenuation, and elastic modulus were measured using a 5-MHz source, 0.6-mm hydrophone, and a waveform digitizer, whereas viscosity, density, and particle size were measured directly. Vehicle showed no significant change with increasing concentration in any of the parameters measured. Perfluoroctylbromide exhibited significant linear increase in viscosity and mass density. Increasing concentrations of PFOB emulsion produced a dramatic linear decrease in velocity (r = .99) and a linear increase in attenuation coefficient, (r = .99). Derived values for bulk modulus (reciprocal of compressibility) also showed significant linear decrease (r = .98) with concentration of PFOB. For typical human in vivo blood concentrations of 3.5% PFOB emulsion, the following values were obtained: density, 1.02 g/mL; viscosity, 10.25 cP; velocity, 1450 m/second; attenuation, 2.8 dB/cm; and bulk modulus, 2.18 GPa. Significant differences were found between PFOB and vehicle at even low concentrations, although particle number and size distributions were the same for each, indicating that the presence of PFOB strongly influences acoustic properties. This enhancement was found to be linear over a wide range of concentrations, which supports the possibility of quantitative analysis.

Acoustics

Expression of a maize cell wall hydroxyproline-rich glycoprotein gene in early leaf and root vascular differentiation.

The spatial pattern of expression for a maize gene encoding a hydroxyproline-rich glycoprotein (HRGP) was determined by in situ hybridization. During normal development of roots and leaves, the expression of the gene was transient and particularly high in regions initiating vascular elements and associated sclerenchyma. Its expression was also associated with the differentiation of vascular elements in a variety of other tissues. The gene encoded an HRGP that had been extracted from the cell walls of maize suspension culture cells and several other embryonic and post-embryonic tissues. The gene was present in one or two copies in different varieties of maize and in the related monocots teosinte and sorghum. A single gene was cloned from maize using a previously characterized HRGP cDNA clone [Stiefel et al. (1988). Plant Mol. Biol. 11, 483-493]. In addition to the coding sequences for the HRGP and an N-terminal signal sequence, the gene contained a single intron in the nontranslated 3' end.

Amino Acid Sequence

Metabolic stability of 3-O-methyl-D-glucose in brain and other tissues.

3-O-Methyl-D-glucose (methylglucose) is often used to study blood-brain barrier transport and the distribution spaces of hexoses in brain. A critical requirement of this application is that it not be chemically converted in the tissues. Recent reports of phosphorylation of methylglucose by yeast and heart hexokinase have raised questions about its metabolic stability in brain. Therefore, we have re-examined this question by studying the metabolism of methylglucose by yeast hexokinase and rat brain homogenates in vitro and rat brain, heart, and liver in vivo. Commercial preparations of yeast hexokinase did convert methylglucose to acidic products, but only when the enzyme was present in very large amounts. Methylglucose was not phosphorylated by brain homogenates under conditions that converted 97% of [U-14C]glucose to ionic derivatives. When [14C]methylglucose, labeled in either the methyl or glucose moiety, was administered to rats by an intravenous pulse or a programmed infusion that maintained the arterial concentration constant and total 14C was extracted from the tissues 60 min later, 97-100% of the 14C in brain, greater than 99% of the 14C in plasma, and greater than 90% of that in heart and liver were recovered as unmetabolized [14C]methylglucose. Small amounts of 14C in brain (1-3%), heart (3-6%), and liver (4-7%) were recovered in acidic products. Plasma glucose levels ranging from hypoglycemia to hyperglycemia had little influence on the degree of this conversion. The distribution spaces for methylglucose were found to be 0.52 in brain and heart and 0.75 in liver.

3-O-Methylglucose

Optimal duration of experimental period in measurement of local cerebral glucose utilization with the deoxyglucose method.

The time course and magnitude of the effects of product loss on the measurement of local cerebral glucose utilization (LCGU) by the 2-[14C]deoxyglucose (DG) method were studied by determination of LCGU in 38 rats with 25-120 min experimental periods after a [14C]DG pulse and in 45 rats with experimental periods of 2.5-120 min during which arterial plasma [14C]DG concentrations (C*P) were maintained constant. LCGU was calculated by the operational equation, which assumes no product loss, with the original set of rate constants and with a new set redetermined in the rats used in the present study; in each case the rate constants were those specific to the structure. Data on local tissue 14C concentrations and C*P were also plotted according to the multiple time/graphic evaluation technique ("Patlak Plot"). The results show that with both pulse and constant arterial inputs of [14C]DG the influence of the rate constants is critical early after onset of tracer administration but diminishes with time and becomes relatively minor by 30 min. After a [14C]DG pulse calculated LCGU remains constant between 25 and 45 min, indicating a negligible effect of product loss during that period; at 60 min it begins to fall and declines progressively with increasing time, indicating that product loss has become significant. When C*P is maintained constant, calculated LCGU does not change significantly over the full 120 min. The "Patlak Plots" reinforced the conclusions drawn from the time courses of calculated LCGU; evidence for loss of product was undetectable for at least 45 min after a pulse of [14C]DG and for at least 60 min after onset of a constant arterial input of [14C]DG.

Animals

Primary structure of the maize NADP-dependent malic enzyme.

Chloroplast-localized NADP-dependent malic enzyme (EC 1.1.1.40) (NADP-ME) provides a key activity for the carbon 4 fixation pathway. In maize, nuclear encoded NADP-ME is synthesized in the cytoplasm as a precursor with a transit peptide that is removed upon transport into the chloroplast stroma. We present here the complete nucleotide sequence for a 2184-base pair full-length maize NADP-ME cDNA. The predicted precursor protein is 636 amino acids long with a Mr of 69,800. There is a strong codon bias found in the amino-terminal portion of NADP-ME that is present in genes for the other enzymes of the C-4 photosynthetic pathway. The NADP-ME transit peptide has general features common to other known chloroplast stroma transit peptides. Comparison of mature maize NADP-ME to the amino acid sequences of known malic enzymes shows two conserved dinucleotide-binding sites. There is a third highly conserved region of unknown function. On the basis of amino acid sequence similarity, the maize chloroplastic enzyme is more closely related to eukaryotic cytosolic isoforms of malic enzyme than to prokaryotic isoforms. We discuss the functional and evolutionary relationship between the chloroplastic and cytosolic forms of NADP-ME.

Amino Acid Sequence

Cell lineage analysis of maize bundle sheath and mesophyll cells.

Maize leaves are divided into repeated longitudinal units consisting of vascular tissue, bundle sheath (BS), and mesophyll (M) cells. We have carried out a cell lineage analysis of these cell types using six spontaneous striping mutants of maize. We show that certain cell division patterns are preferentially utilized, but not required, to form the characteristic arrangement of cell types. Our data suggest that early in development a central cell layer is formed, most frequently by periclinal divisions in the adaxial subepidermal layer of the leaf primordium. Lateral and intermediate veins are initiated in this central layer, most often by divisions which contribute daughter cells to both the procambium and the ground meristem. These divisions generate "half vein" units which comprise half of the bundle sheath cells around a vein and a single adjacent M cell. We show that intermediate veins are multiclonal both in this transverse direction and along their lengths. BS cells are more closely related to M cells in the middle layer of the leaf than to those in the upper and lower subepidermal layers. An examination of sector boundaries has shown that photosynthetic differentiation in M cells is affected by the phenotype of neighboring BS cells.

Cell Differentiation