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Biomedical subjects

A L Wilson

Publications and source records attributed to A L Wilson.

At least 19 recordsLinked to original sources

Synthesis of a yohimbine-agarose matrix useful for large-scale and micropurification of multiple alpha 2-receptor subtypes.

We have provided a detailed protocol for the synthesis of a yohimbine-agarose matrix that has been shown to be effective for isolation of the alpha 2A-adrenergic receptor from human platelet and purification of the alpha 2A-adrenergic receptor to apparent homogeneity from porcine brain cortex using chromatography on only two sequential yohimbine-agarose columns. In addition, this affinity matrix also interacts with alpha 2 receptors of the alpha 2B subtype extracted from cultured NG108-15 cells. Finally, this affinity matrix has proven useful for monitoring posttranslational modifications of the receptor in digitonin extracts of metabolically labeled cells. Thus, this affinity matrix can be exploited for the purification of multiple alpha 2-adrenergic receptor subtypes on both a macro- and microscale and should be of value to any laboratory exploring the molecular basis for alpha 2-adrenergic functions.

Adrenergic alpha-Agonists

Does prenatal care decrease the incidence and cost of neonatal intensive care admissions?

This study was conducted to examine the potential effects of expanded Medicaid coverage for low income women. Statewide birth data for 1983 to 1985 were examined to determine the relationship between prenatal care and admissions to neonatal intensive care units (NICUs) and the costs of this care. An NICU sample was constituted from infants who were discharged live following more than 7 NICU days, were referred to an out of state tertiary center, or died following NICU admission. Inadequate care (no prenatal care, only last trimester care, or less than five visits) was received by 11% of the total birth cohort and by 18% of the infants in the NICU sample (p less than 0.001). Infants with inadequate care had a NICU admission rate of 5.10% versus 2.86% for those with adequate prenatal care (p less than 0.001). The hospital billings for infants in the NICU sample with inadequate care were significantly higher than were those for infants with adequate care (p less than 0.05). Assuming that economic resources limit access to prenatal care, the projection can be made that had all women with inadequate prenatal care received Medicaid-covered adequate prenatal care, expenditure for this care would yield more than a two to one return in savings in NICU costs.

Adolescent

Novel amiloride analog allosterically modulates the alpha 2-adrenergic receptor but does not inhibit Na+/H+ exchange.

Two novel amiloride analogs have been synthesized during the course of efforts to develop a photoaffinity label for the amiloride allosteric domain on alpha 2-adrenergic receptors. One of these, 5-[N-2'-aminoethyl-N'-isopropyl]amiloride-N-[4"-azidosalicylamide] (A-EIA-AS), markedly accelerates the rate of dissociation of [3H]yohimbine from affinity-purified alpha 2-adrenergic receptors, an assay for allosteric modulation of receptor-adrenergic ligand interactions. In contrast, this agent does not appreciably inhibit Na+/H+ exchange, measured as 5-(N-ethyl-N-isopropyl)amiloride (EIA)-inhibitable 22Na+ uptake into cultured renal epithelial cells. A second analog, 5-[N-2'-(4"-azidosalicylamidino)ethyl-N'- isopropyl]amiloride (ASA-EIA), does not foster an accelerated rate of dissociation of [3H]yohimbine binding from the alpha 2 receptor but does block the ability of A-EIA-AS to do so, suggesting that ASA-EIA and A-EIA-AS interact at a common binding site. Interestingly, the ability of EIA to accelerate [3H]yohimbine dissociation is not blocked by ASA-EIA, a finding that may indicate that EIA and A-EIA-AS allosterically modulate alpha 2 receptor-ligand interactions via distinct or nonoverlapping binding sites.

Amiloride

The state of South Dakota's child: 1991.

This annual report describes the continuing trend of a decreasing birth rate in South Dakota. Infant mortality data show that South Dakota's neonatal mortality rates continue to be below those of the nation and post neonatal mortality rates exceed those of the United States. A very high Native American post neonatal mortality rate persists. Low birth weight contributes to approximately three quarters of newborn deaths and has declined by approximately 1% over the past two and one half decades. Descriptions of preterm labor prevention programs are presented with an emphasis upon the need for education of pregnant women and communities about its risk factors and warning signs. A review of a variety of new programs that aim to improve maternal and child health in South Dakota is provided.

Birth Rate

Monovalent cation and amiloride analog modulation of adrenergic ligand binding to the unglycosylated alpha 2B-adrenergic receptor subtype.

The unglycosylated alpha 2B subtype of the alpha 2-adrenergic receptor found in NG-108-15 cells possesses allosteric regulation of adrenergic ligand binding by monovalent cations and 5-amino-substituted amiloride analogs. These findings demonstrate that allosteric modulation of adrenergic ligand binding is not a property unique to the alpha 2A subtype. The observation that amiloride analogs as well as monovalent cations can modulate adrenergic ligand binding to the nonglycosylated alpha 2B subtype indicates that charge shielding due to carbohydrate moieties does not play a role in this allosteric modulation but, rather, these regulatory effects result from interactions of cations and amiloride analogs with the protein moiety of the receptor. Furthermore, the observation that both alpha 2A and alpha 2B receptor subtypes are modulated by amiloride analogs suggests that structural domains that are conserved between the two are likely to be involved in this allosteric modulation.

Amiloride

The state of South Dakota's child: 1990.

For the first time since 1970 the birth rate in South Dakota (15.7) has dropped to a rate level lower than that of the nation (15.9). The continuing decline in the number of total births in South Dakota makes it all the more important to be cautious as annual South Dakota data are examined. Five year (1984-1988) mean neonatal mortality data show that its rate for both the white and the nonwhite populations in South Dakota are lower than those of the nation. Alternately, the five year mean post neonatal mortality rate for whites is slightly above the national rate and for nonwhites it is substantially higher than the national rate. This paper concludes with a discussion of approaches currently being pursued in the state to improve the health and well being of Native American children.

Adolescent

An aspartate conserved among G-protein receptors confers allosteric regulation of alpha 2-adrenergic receptors by sodium.

The residue involved in sodium regulation of G-protein-coupled receptors has been identified by site-directed mutagenesis of the alpha 2-adrenergic receptor gene. Mutation of Asp-79 to Asn-79 entirely eliminates allosteric regulation of ligand binding by monovalent cations without perturbing the selectivity of adrenergic binding or allosteric modulation of that binding by amiloride analogs. The high degree of conservation of this aspartate residue in all G-protein-coupled receptors, without even a conservative change to glutamate, underscores the probable importance of this allosteric regulation.

Affinity Labels

Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs.

The gene for an alpha 2-adrenergic receptor has been cloned from a porcine genomic library, using as a probe a 0.95-kilobase Pst fragment of the gene for the human platelet alpha 2-adrenergic receptor. The identity of the cloned porcine gene was confirmed initially on the basis of partial amino acid sequence information obtained following cyanogen bromide digestion of homogeneous preparations of porcine brain alpha 2-adrenergic receptors. The deduced amino acid sequence for the porcine receptor, when compared to other members of the family of guanine nucleotide-binding protein-coupled receptors, shares the same overall structural characteristics and most closely resembles the human platelet C10 alpha 2-adrenergic receptor (greater than 93% homology). The putative porcine alpha 2-receptor gene was expressed in the COS-M6 cell line. Transfected cells display saturable [3H]yohimbine binding. The KD for [3H]yohimbine, determined in digitonin-solubilized preparations, is 5.8 nM. The selectivity of agonists and antagonists in competing for [3H]yohimbine binding to membranes prepared from the transfected cells is characteristic of the alpha 2A subtype of adrenergic receptors. The porcine alpha 2-receptor also was expressed permanently in LLC-PK1 porcine kidney cells at a level of 100 pmol/mg protein. The alpha 2-agonist UK14304 is able to attenuate forskolin or vasopressin-stimulated cAMP accumulation by at least 50% in these cells. Allosteric modulation of [3H] yohimbine binding by Na+, H+, and 5-amino-substituted analogs of amiloride also was demonstrated for the alpha 2-receptor expressed in COS-M6 cells. Moreover, these modulatory effects were quantitatively similar to those observed for homogeneous preparations of the alpha 2-receptor purified from porcine brain cortex. Retention of the effects of cations and amiloride analogs in transiently expressed alpha 2-receptors supports the interpretation that the allosteric sites for these agents reside in the alpha 2-receptor molecule itself.

Allosteric Regulation

The hydrophobic tryptic core of the porcine alpha 2-adrenergic receptor retains allosteric modulation of binding by Na+, H+, and 5-amino-substituted amiloride analogs.

Extensive trypsinization of the purified alpha 2-adrenergic receptor and repurification by wheat germ agglutinin-agarose chromatography yields an adrenergic ligand-binding hydrophobic core of the receptor. Allosteric modulation of adrenergic ligand binding by Na+, H+, and 5-amino-substituted analogs of amiloride is quantitatively retained in this core, as assessed by the ability of these agents to accelerate the rate of [3H] yohimbine dissociation from the adrenergic ligand-binding site. These findings refine our understanding of where within the alpha 2-adrenergic receptor structure these allosteric agents bind and, for the effects of Na+ and H+, allow certain predictions to be made as to which carboxylic acid side chains are probable candidates for participation in a monovalent cation-binding pocket within the hydrophobic tryptic core of the receptor.

Allosteric Regulation

Mothers' behavior with home infant apnea monitors.

This study presents findings from 35 interviews with mothers of infants who were monitored for apnea following discharge from the same neonatal intensive care unit. The interviews took place at a mean of 28 weeks following discontinuation of the infant home apnea monitor and focused upon the mothers' behavior with the monitor. One family had independently ceased to use the monitor within 1 week of their infant's hospital discharge. All other mothers reported always having used the monitor at night, and 92% always used it during their infants' daytime naps. Approximately one half of the mothers would not have been able to consistently hear an alarm, however, when their infant was asleep. Consistency of availability to a monitored infant was not related to the mothers' background, attitudes, or experiences with their infant. These data indicate the need to emphasize for all caregivers the importance of being available to their monitored infant at all times.

Adult

The state of South Dakota's child: 1989.

The 1987 infant mortality in South Dakota returned to a rate below that of the nation as had been the trend for the eight years prior to 1986. Comparisons of South Dakota and the United States data show that for both whites and non whites the mean five year neonatal mortality rates were below those of the nation. Alternately, the South Dakota white post neonatal mortality rate is slightly higher than that of the nation and the non white post neonatal mortality rate is more than three times higher than that of the United States. Comparisons of the causes of post neonatal deaths show that the relative risk of death from potentially preventable causes is four times higher among South Dakota non whites as whites. The paper concludes with a discussion of the incidence of child abuse and neglect and the important role health care providers may play in preventing and treating this cause of significant mortality and morbidity of children.

Child

PharmaTrend as a management tool: introduction.

Use of the PharmaTrend computerized management information system to document workload and productivity in hospital pharmacy departments is described. PharmaTrend provides indicators in the areas of revenue, cost, drug distribution, clinical services, research, education, and management support; examples are total direct cost per admission, total drug cost per drug distribution work unit, and comparisons between cost and revenue, supportive staff and pharmacist work hours, and total staff work and paid hours. The key information provided by PharmaTrend is not specific indicators or values, however, but the display of trends. PharmTrend files can be downloaded to other spreadsheet and database management programs; the sophisticated user can recalculate values for indicators or develop new indicators. Information about revenue and the cost of drug distribution is easily obtained from reports; this information, combined with data on hours worked to provide drug distribution services, can provide access to all the key PharmaTrend indicators. Institution-specific data are made available to managers elsewhere by submitting them for use in the PharmaTrend national report, which is organized so that users can compare values for their indicators with those reported by hospitals of various size in various geographic regions. PharmaTrend can be a valuable tool in hospital pharmacy management and provides a basis for developing accurate and meaningful workload standards for pharmacy practice.

Database Management Systems

The next baby: parents' responses to perinatal experiences subsequent to a stillbirth.

This study examines the responses experienced in the perinatal period by parents who have had an infant subsequent to a stillbirth. Interview findings from eight couples in a stillbirth study group (SSG) who had this experience and eight couples in a comparison group (CG) whose live-born children were delivered at similar time intervals as the SSG were compared. In contrast to a comparison group, half of the SSG mothers did not make preparations for their babies until after delivery and seven of eight SSG mothers wanted the hospital staff to recognize their previous loss and give them special understanding. The parents in the SSG reported that because of their loss, they were likely to spend more time (p less than 0.01), to be more attentive to fussing (p less than 0.01), and to hold their babies more (p less than 0.01). Over half of the SSG parents also noted that after having another baby, they experienced greater relaxation, happiness, and closeness with their spouse. After their subsequent baby, the SSG parents observed that thinking about the stillbirth was easier, but resented being told by others to feel grateful.

Adaptation, Psychological

Characterization of histamine type 1 receptors on natural suppressor lymphoid cells.

Using the radioligand H1 antagonist [3H]pyrilamine, we have characterized the histamine type 1 receptor on cloned murine natural suppressor cells (NS). A single, specific binding site for [3H]pyrilamine exists on these cells. The binding was saturable and reversible by various specific H1 receptor antagonists. The rank order of potency for displacement of [3H]pyrilamine binding from the H1 receptor by H1 receptor antagonists was promethazine = pyrobutamine greater than pyrilamine greater than diphenhydramine greater than chlorpheniramine. The histamine type-2 agonists, impromidine and dimaprit, and antagonists, cimetidine and ranitidine, as well as selected non-histamine agonists, did not displace [3H]pyrilamine from its binding sites on the natural suppressor cells. The data indicate that the theoretical KD was 1.1 +/- 0.3 X 10(-7) M while the measured KD of binding for [3H]pyrilamine was 6.0 +/- 0.8 X 10(-8) M; the maximum binding was 4.13 nM and the number of binding sites/cell was 2.14 +/- 0.29 X 10(6) (N = 3).

Animals

Mothers and their children look at baby pictures: the NICU experience in retrospect.

Photographs of Neonatal Intensive Care Unit (NICU) patients are frequently given to parents to promote bonding, but little attention has been paid to how families respond years later to viewing these special baby pictures. This study examines how 71 mothers of 3 to 7-year-old developmentally normal (DQ greater than or equal to 80) children who weighed less than 1,500 g at birth describe this experience. Compared to a group of mothers whose children were full term at birth, the NICU mothers described personally feeling and perceiving their children as more fearful (p less than .05), inquisitive (p less than .0001), worried (p less than .01), thoughtful (p less than .0001), and tearful (p less than .05). The responses of NICU mothers were significantly more highly correlated with their perceptions of their children's responses than were the mother-child correlations observed in a comparison group. The NICU children were reported by their mothers to ask about the NICU equipment, pain, being alone, their physical scars, and if their being "bad" caused their need for intensive neonatal care. Recommendations are provided on how pediatric care providers can assist NICU parents anticipate questions and respond to their children's concerns as they view these potentially distressing photographs.

Adult

What changes can health promotion achieve and how long do these changes last? The trade-offs between expediency and durability.

This article examines the logic and evidence by which health education together with related organizational, economic, and environmental supports or interventions can result in more than superficial or transitory adjustments of behavior conductive to health. Most signs point to continuing development of the health promotion movement, as indicated by its grass roots origins, the long-range convergence of changes in health-related behaviors (e.g., smoking, diet, exercise, alcohol consumption, safety practices), public and private sector investment, and the growing interest of hospitals and medical practitioners in health promotion. To assess the durability of behavior changes accomplished through health promotion activities, the apparent discrepancy between improvements observed on the social level and high relapse rates reported in most experimental studies on individuals is analyzed, leading to the conclusion that the experimental studies have overstated the problem of relapse. There is a trade-off between expedient interventions that achieve short-term behavior changes and more difficult, slower-acting educational and lifestyle interventions that assure a greater congruence between the behavior and the values, beliefs, and circumstances of the individual.

Behavior

State reporting of live births of newborns weighing less than 500 grams: impact on neonatal mortality rates.

The National Center for Health Statistics reports that in 1983 65% of all infant deaths in the United States occurred in the neonatal period. Of these reported neonatal deaths, 17% were of infants weighing less than 500 g at birth. There was, however, variation in state-reported incidence of live births of newborns in this weight cohort (0.2 to 2.2 per 1,000 live births). The states with the lowest neonatal mortality rate have the lowest incidence of birth weights less than 500 g (rho = .77). If it is assumed that mortality for this weight category is nearly 100%, there is marked variation (5% to 32%) in the contribution of this weight cohort to a state's total neonatal mortality rate. Contributing to this variation may be definitions of live birth used by states. The World Health Organization defines a live birth as the product of conception showing signs of life "irrespective of the duration of pregnancy" and this definition is used by 33 states. Only one state (Ohio) includes the gestational criteria of "at least 20 weeks" in its definition of live birth. There is evidence to suggest that definitions are not uniformly used within individual states. For example, in 1983, 20 states did not report any live births with weights less than 500 g among their "other" populations of nonwhite, nonblack residents. Half of these states, however, use the World Health Organization definition of live birth. Despite the exclusionary wording in Ohio's definition of liver birth, 16% of newborns who died in that state had birth weights less than 500 g.(ABSTRACT TRUNCATED AT 250 WORDS)

Female