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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
PubMed2006

Differential expression of photoreceptor-specific genes in the retina of a zebrafish cadherin2 mutant glass onion and zebrafish cadherin4 morphants.

Cadherins are Ca2+ -dependent transmembrane molecules that mediate cell-cell adhesion through homophilic interactions. Cadherin2 (also called N-cadherin) and cadherin4 (also called R-cadherin), members of the classic cadherin subfamily, have been shown to be involved in development of a variety of tissues and organs including the visual system. To gain insight into cadherin2 and cadherin4 function in differentiation of zebrafish photoreceptors, we have analyzed expression patterns of several photoreceptor-specific genes (crx, gnat1, gnat2, irbp, otx5, rod opsin, rx1, and uv opsin) and/or a cone photoreceptor marker (zpr-1) in the retina of a zebrafish cadherin2 mutant, glass onion (glo) and in zebrafish embryos injected with a cadherin4 specific antisense morpholino oligonucleotide (cdh4MO). We find that expression of all these genes, and of zpr-1, is greatly reduced in the retina of both the glo and cadherin4 morphants. Moreover, in these embryos, expression of some genes (e.g. gnat1, gnat2 and irbp) is more affected than others (e.g. rod opsin and uv opsin). In embryos with both cadherins functions blocked (glo embryos injected with the cdh4MO), the eye initially formed, but became severely and progressively disintegrated and expressed little or no crx and otx5 as development proceeded. Our results suggest that cadherin2 and cadherin4 play important roles in the differentiation of zebrafish retinal photoreceptors.

Animals↗
PubMed2004

Energy-scavenging amplifiers for miniature solid-state lasers.

Longitudinally pumped miniature lasers are inefficient, partly because of their inefficient absorption of the pump light. Scavenging the unabsorbed pump light to pump an in-line amplifier can greatly enhance the efficiency of the system, with minimal added cost, size, or complexity.

Journal Article↗
PubMed2004

Cadherin-2 and cadherin-4 in developing, adult and regenerating zebrafish cerebellum.

Cadherins are cell adhesion molecules that regulate development of a variety of tissues and maintenance of adult structures. In this study, we examined expression of two zebrafish classical cadherins, cadherin-2 and cadherin-4, in the cerebellum of developing, normal adult, and regenerating adult zebrafish using in situ hybridization and immunohistochemical methods. Cadherin-2 was widely expressed by the cerebellum of embryonic (24-50-h post fertilization) and larval zebrafish (3-14 days). Cadherin-2 expression became much reduced in the adult cerebellum, but it was greatly up-regulated in the regenerating adult cerebellum. Cadherin-4 was not detected in the embryonic cerebellum, but it was expressed in the Purkinje cells of the larval and adult cerebellum. To gain insight into cadherin-2 role in the formation of the cerebellum, we analyzed embryos injected with a specific cadherin-2 antisense morpholino oligonucleotide (cdh2MO1), and found that the cerebellar development of the cdh2MO1-injected embryos was severely disrupted. This phenotype was confirmed by examining a cadherin-2 mutant, glass onion. Our results suggest that cadherins are crucial for the normal development of the zebrafish cerebellum, and they may also be involved in the regeneration of injured fish cerebellum.

Animals↗
PubMed2001

Membrane targeting of a Rab GTPase that fails to associate with Rab escort protein (REP) or guanine nucleotide dissociation inhibitor (GDI).

The targeting of various Rab proteins to different subcellular compartments appears to be determined by variable amino acid sequences located upstream from geranylgeranylated cysteine residues in the C-terminal tail. All nascent Rab proteins are prenylated by geranylgeranyltransferase II, which recognizes the Rab substrate only when it is bound to Rab escort protein (REP). After prenylation, REP remains associated with the modified Rab until it is delivered to the appropriate subcellular membrane. It remains unclear whether docking of the Rab with the correct membrane is solely a function of features contained within the prenylated Rab itself (with REP serving as a "passive" carrier) or whether REP actively participates in the targeting process. To address this issue, we took advantage of a mutation in the alpha2 helix of Rab1B (i.e. Y78D) that abolishes REP and GDI interaction without disrupting nucleotide binding or hydrolysis. These studies demonstrate that replacing the C-terminal GGCC residues of Rab1B(Y78D) with a CLLL motif permits this protein to be prenylated by geranylgeranyltransferase I but not II both in cell-free enzyme assays and in transfected cells. Subcellular fractionation and immunofluorescence studies reveal that the prenylated Rab1B(Y78D)CLLL, which remains deficient in REP and GDI association is, nonetheless, delivered to the Golgi and endoplasmic reticulum (ER) membranes. When the dominant-negative S22N mutation was inserted into Rab1B-CLLL, the resulting monoprenylated construct suppressed ER --> Golgi protein transport. However, when the Y78D mutation was added to the latter construct, its inhibitory effect on protein trafficking was lost despite the fact that it was localized to the ER/Golgi membrane. Therefore, protein interactions mediated by the alpha2 helical domain of Rab1B(S22N) appear to be essential for its functional interaction with components of the ER --> Golgi transport machinery.

Adaptor Proteins, Signal Transducing↗
PubMed2001

State of South Dakota's child: 2000.

For the second consecutive year, 1999 brought an increase in the total number of births in South Dakota. Low birth weight newborns also increased during this year to 5.9%, representing the highest rate observed since 1974. Although the total percent of low birth weight increased, the percent of very low birth weight slightly decreased. Also observed is an increase in the use of prenatal care in the first trimester of pregnancy. The infant mortality rate for the state decreased slightly but remains higher than what is noted nationally. The rate of neonatal mortality is also slightly higher than the national rate. South Dakota's rate of post neonatal mortality remains considerably higher than the national rate but did decrease in 1999. The special topic of this year's report is brain development and the role of early experience. The state's new Bright Start program for pregnant women and their infants is described.

Birth Rate↗
PubMed2000

Acute and chronic toxicity of the herbicide benzofenap (Taipan 300) to Chironomus tepperi Skuse (Diptera: Chironomidae) and Isidorella newcombi (Adams and Angas) (Gastropoda: Planorbidae).

Acute and chronic toxicity tests were conducted on the herbicide benzofenap (Taipan 300) using two Australian freshwater invertebrates. The commercial formulation of benzofenap and a blank formulation containing only the adjuvants of Taipan 300 were tested against final instar larvae of the midge Chironomus tepperi and adults of the aquatic snail Isidorella newcombi. In 24-h acute bioassays the midge larvae did not show significant mortality at a nominal concentration of 1.2 mg/L active ingredient (AI), double the maximum notional concentration expected in rice fields after application of Taipan 300 at the permit rate of 2 L/ha. No significant snail mortality was recorded in acute bioassays (24-h exposure, 48-h recovery) at nominal concentrations up to 76 mg/L AI, which is over 120 times the maximum notional field concentration. In chronic assays, the pupation and emergence of C. tepperi was monitored after a 4-h pulse exposure of final instar larvae to Taipan 300 (nominal concentrations 0.001 to 0.1 mg/L AI) and adjuvant-only (0.1 mg/L equivalent) treatments. No statistically significant effects were observed, although emergence appeared to be delayed by higher benzofenap concentrations and by the adjuvant-only treatment. During snail bioassays, egg and feces production were monitored for 21 days after 24-h exposure to Taipan 300 (nominal concentrations 1.2 mg/L to 60 mg/L AI) and adjuvant-only treatments (60 mg/L equivalent). No significant chronic effects were proven against I. newcombi, despite a decline in egg mass production following exposure to all treatments and a reduction in the total numbers of eggs produced at the highest nominal concentrations tested (60 mg/L AI and adjuvant-only treatments). Similarly, feces production by snail pairs exposed to the majority of treatments declined, but these differences were not statistically significant. It is concluded that Taipan 300 does not represent a significant risk to mature C. tepperi larvae or adult I. newcombi in downstream environments when applied to rice fields at the permit rate of 2 L/ha.

Acetophenones↗
PubMed2000

The Balanced Budget Act: potential implications for the practice of vascular surgery.

PURPOSE: Previous study results have shown a favorable impact on stroke rate with an increasing hospital volume of carotid endarterectomies (CEAs). This is not only the most frequently performed peripheral vascular procedure in the United States but also perhaps the most widely dispersed procedure relative to hospital type. Medical centers have adopted various strategies to lower the cost of hospitalization by reducing the length of stay (LOS), the major component of hospital cost. By 2002, the Balanced Budget Act is projected to reduce Medicare provider payments to academic medical centers (AMCs) by 15.5%, a reduction that is twice that for minor or nonteaching hospitals. We assessed the relationships between hospital costs, CEA volume, and stroke-mortality rates in AMCs and non-AMCs in Massachusetts. METHODS: With patient level data from the Massachusetts Division of Health Care Finance and Policy and with hospital cost and charge reports from the Health Care Financing Administration, HealthShare Technology provided data for all the patients discharged from a Massachusetts hospital who underwent CEA (n = 10,211) during the fiscal years 1995, 1996, and 1997, including cost, LOS, and disposition. The outcomes were further defined with in-hospital stroke and mortality rates. Five high volume AMCs (HVAMCs) were compared with all other nonacademic hospitals, which were further subdivided by annual volume into high volume non-AMCs (> or =50 cases), medium volume non-AMCs (24-49 cases), and low volume non-AMCs (12-23 cases). Statistical analysis was performed with analysis of variance to compare the means of all the cost and LOS data, and chi(2) test was used for comparison of incidence (significance assumed for P < or =. 05). RESULTS: Hospital costs were comparable among the four hospital types during individual years and averaged $6200, but HVAMCs were significantly more expensive overall, with a mean cost of $7882. The only centers to decrease their costs during the years evaluated were the HVAMCs, from $8706 to $6784. Length of stay did not differ among the groups in any year or overall, with a mean of 3.8 days, but did decrease between years at HVAMCs from 3.9 to 2.5 days. The combined stroke-mortality rates were significantly less at the HVAMCs (0.9%) than at either the high volume non-AMCs (1.9%) or the medium volume non-AMCs (2.5%). There was no significance in the analysis results of all the data within the low volume non-AMCs. CONCLUSION: Patients in HVAMCs have the best outcomes after CEA. Despite the achievement of significant efficiencies, AMCs have a small cushion to reduce further either LOS or resources to maintain a competitive cost position and to compensate for the fixed expenses of academic medicine. The Balanced Budget Act raises an equity concern for AMCs because it differentially affects the centers with the best outcomes. The financial implication of this may be a direct incentive for procedures to be done in centers with less optimal outcomes.

Academic Medical Centers↗
PubMed2000

State of South Dakota's child: 1999.

The Surgeon General's Year 2000 health goals for the nation are presented and data from South Dakota and the United States that measure progress toward achieving them are discussed. The percentage of low-birth weight babies (LBW) in South Dakota is lower than observed nationally, but, similar to the national trend, has increased in the past few years. Between 1996-1998, 1.1% of all newborns in the state weighed less than 1500 grams, and 5.7% weighed less than 2500 grams. There has been continuing progress observed in the survival rate of the very low birth weight infant. In 1996 the state experienced a precipitous drop in its infant mortality rate (IMR) that has not been sustained in the past two years. The state's 1998 IMR of 9.0 per 1000 live births, however, is less than the mean rate of 10 that persisted over the previous decade. The IMR for white babies (5.7) has achieved the Year 2000 Goal. The rate of Sudden Infant Death in South Dakota is significantly higher (p < .001) than that observed nationally and speaks to the importance of placing babies on their backs to sleep and education regarding the risks associated with exposing a fetus and baby to smoking. The special topic of this year's report is breast-feeding. The benefits of breast-feeding to babies and mothers are described, as well as the need for it to be advocated by the health care community. This advocacy must emphasize breast-feeding's importance, how women can be assisted as they begin to nurse, and how community efforts can be taken to enable breast-feeding continuation when women return to work following delivery.

Birth Rate↗
PubMed1999

The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic usage.

The rectal carriage of glycopeptide-resistant Enterococcus spp. (GRE) had been established at approximately 50% in a series of prevalence studies on a busy haematological malignancy unit. The aim of this study was to reduce the chance of patients acquiring GRE. A prospective three-phase sequential study was performed. In Phase 1, the acquisition rate of GRE detectable by rectal swab was measured without any intervention for a period of 4 months. For the following 8 months (Phase 2), the first-line treatment for febrile neutropenic episodes was changed from monotherapy with ceftazidime to piperacillin/tazobactam. In addition, an intense education programme was introduced to improve hygiene to reduce the risk of case-to-case spread. In the final 4 months (Phase 3), ceftazidime was again used as the first-line antimicrobial, while continuing the same level of training in relation to hygiene. The carriage of GRE was measured from rectal swabs done weekly. During the initial 4 months, at any time, 40-50% of patients in the unit were colonized with GRE, and 43 of 75 (57%) new patients initially negative for GRE acquired it within 6 weeks of their admission. In Phase 2, 25 patients out of 129 (19%) acquired GRE, with the acquisition rate falling progressively so that in the last 3 months, only one new patient acquired GRE (logrank comparison of probabilities for cohort 1 vs cohort 2b: P < 0.0001). A return to ceftazidime in Phase 3 was associated with a return of the risk of acquiring detectable GRE colonization, despite continued hygiene teaching and surveillance, with 21 out of 58 patients (36%) acquiring GRE (cohort 1 vs cohort 3: P = 0.08). Glycopeptide usage was not reduced during the period of the study. Clinical cases were seen only in Phases 1 and 3. Although the reduction in the risk of acquiring GRE may have been due in part to hygiene practices as well as to the change in antimicrobial usage, or may have occurred spontaneously for other reasons, the return of the problem with the reintroduction of ceftazidime strongly suggests that this antibiotic was responsible for encouraging the acquisition of detectable GRE.

Adolescent↗
PubMed1999

State of South Dakota's child: 1998.

Births in South Dakota again decreased in 1997, continuing an ongoing trend that began in 1980. Progress in 1997 was noted in the use of first trimester prenatal care and the rate of low birth weight in the State remained lower than that observed nationally. The State's infant mortality rate for 1997 showed a continuation of the favorable shift in rates of the last decade that was initiated with the progress observed in 1996. Smoking and drinking during pregnancy is higher in South Dakota than noted nationally. How and why substance abuse prevention efforts must begin during childhood is discussed in this review. Currently, the rates of smoking and alcohol use are higher among South Dakota teens than noted nationally, and have increased over the past six years. Approaches to preventing substance abuse for the sake of the health and well being of youth and their potential future children are presented.

Adolescent↗
PubMed1998

Prenylation of Rab8 GTPase by type I and type II geranylgeranyl transferases.

Rab GTPases are post-translationally modified by addition of geranylgeranyl moieties to carboxyl-terminal cysteine residues. For Rab proteins ending with xxCC xCxC and CCxx motifs this modification is catalysed by geranylgeranyltransferase type II (GGTaseII), and is entirely dependent on the Rab substrate being bound to Rab escort protein (REP). Several Rab proteins contain carboxyl-terminal CaaL prenylation motifs typical of members of the Rho family, which are modified in a REP-independent manner by geranylgeranyltransferase type I (GGTaseI). The present studies show that one such Rab protein (Rab8), which ends with a CVLL motif, is uniquely able to serve as a substrate for either REP/GGTaseII or GGTaseI in cell-free assays. The modification of Rab8 by GGTaseI did not require REP, indicating that a REP-induced conformational change is not essential for exposure of the Rab carboxyl-terminal cysteine prenylation site. To determine whether one enzyme plays a predominant role in Rab8 prenylation in vivo, the incorporation of [3H]mevalonate into Rab8 was measured in human embryonal kidney 293 cells under conditions where the activity of GGTaseI, but not GGTaseII, was blocked by the peptidomimetic inhibitor GGTI-298. The GGTaseI inhibitor did not prevent prenylation of either overexpressed Myc-tagged Rab8 or endogenous Rab8, whereas prenylation of a known GGTaseI substrate with the same carboxyl-terminal motif, Cdc42Hs, was completely blocked. To rule out the possibility that the apparent prenylation of Rab8 by GGTaseII occurs only when GGTaseI activity is eliminated, metabolic labelling studies were carried out in the absence of the GGTaseI inhibitor, using a REP-binding-deficient Rab8 construct (Y78D) that cannot serve as a substrate for GGTaseII, but is indistinguishable from wild-type Rab8 as a substrate for GGTaseI. Prenylation of the Y78D mutant was reduced by 60-70% in intact cells, consistent with the conclusion that the majority of Rab8 is prenylated by the REP/GGTaseII system in vivo.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The putative "switch 2" domain of the Ras-related GTPase, Rab1B, plays an essential role in the interaction with Rab escort protein.

Posttranslational modification of Rab proteins by geranylgeranyltransferase type II requires that they first bind to Rab escort protein (REP). Following prenylation, REP is postulated to accompany the modified GTPase to its specific target membrane. REP binds preferentially to Rab proteins that are in the GDP state, but the specific structural domains involved in this interaction have not been defined. In p21 Ras, the alpha2 helix of the Switch 2 domain undergoes a major conformational change upon GTP hydrolysis. Therefore, we hypothesized that the corresponding region in Rab1B might play a key role in the interaction with REP. Introduction of amino acid substitutions (I73N, Y78D, and A81D) into the putative alpha2 helix of Myc-tagged Rab1B prevented prenylation of the recombinant protein in cell-free assays, whereas mutations in the alpha3 and alpha4 helices did not. Additionally, upon transient expression in transfected HEK-293 cells, the Myc-Rab1B alpha2 helix mutants were not efficiently prenylated as determined by incorporation of [3H]mevalonate. Metabolic labeling studies using [32P]orthophosphate indicated that the poor prenylation of the Rab1B alpha2 helix mutants was not directly correlated with major disruptions in guanine nucleotide binding or intrinsic GTPase activity. Finally, gel filtration analysis of cytosolic fractions from 293 cells that were coexpressing T7 epitope-tagged REP with various Myc-Rab1B constructs revealed that mutations in the alpha2 helix of Rab1B prevented the association of nascent (i.e., nonprenylated) Rab1B with REP. These data indicate that the Switch 2 domain of Rab1B is a key structural determinant for REP interaction and that nucleotide-dependent conformational changes in this region are largely responsible for the selective interaction of REP with the GDP-bound form of the Rab substrate.

Adaptor Proteins, Signal Transducing↗
PubMed1998

State of South Dakota's Child: 1997.

The total number of live births in South Dakota in 1996 (10,469) was nearly identical to that reported in 1995, showing a stabilization in the 19% decrease in births noted between 1980 and 1993. Following a decade of little progress in improving the state's infant mortality rate, 1996 showed a significant (p < .05) decrease in this rate from its previous five year mean of 9.5 infant deaths per 1,000 live births. The 60 infant deaths in the state in 1996 yield an infant mortality rate of 5.7, much lower than the 7.2 rate noted nationally. From previous five year mean rates, the total neonatal mortality rate decreased by 42% and the post neonatal rate decreased by 34%. Decreases were noted during each of these periods of infancy for both white newborns and those of color. In 1996 there was a decrease from the mean 1993-95 rate of perinatal causes of infant death (e.g. short gestation, respiratory distress syndrome) for all populations of infants in South Dakota. For white infants there was a decrease in the rate of Sudden Infant Death Syndrome and of deaths due to congenital anomalies. For American Indians there was a decrease in the rate of infant deaths due to injuries. As the total number of births is small in South Dakota, caution must always be exercised as data from one year are examined. Time will tell if the decrease in infant mortality noted in 1996 signals a new trend. Recognizing the need for communities to examine the unique causes and circumstances of childhood deaths in their local areas, the concept of infant and child mortality committees is discussed as a means of initiating prevention activities that protect young life.

Black or African American↗
PubMed1997

Computerized medication administration records decrease medication occurrences.

Studies have demonstrated that medication errors occur at a number of locations in the continuum between ordering of drug therapy and administration of the medication. Computer management of patient medication profiles offers the opportunity to enhance communication between pharmacists and nurses, and to decrease medication errors and delays in delivery of therapy. A number of authors have postulated that computerization of medication profiles would enhance medication delivery accuracy and timeliness, but no study has demonstrated this improvement. We report the results of a retrospective analysis undertaken to assess the improvements resulting from sharing a computerized medication record. We used a broader definition of medication occurrences that includes the more traditional definition, and averted errors, delays in delivery of medications and information, and disagreements between pharmacy and nursing medication profiles. We compared medication occurrences reported through an existing internal system between two periods; the first when separate pharmacy and nursing medication records were used, and the second period when a shared medication record was used by pharmacy and nursing. Average medication occurrences per admission decreased from 0.1084 to 0.0658 (p < 0.01). Medication occurrences per dose decreased from 0.0005 to 0.0003 (p < 0.01). The use of a shared medication record by pharmacy and nursing led to a statistically significant decrease in medication occurrences. Information shared between the two professions allowed timely resolution of discrepancies in medication orders, leading to better execution of drug therapy, decreased medication occurrences, and increased efficiency.

Clinical Pharmacy Information Systems↗
PubMed1997

State of South Dakota's child: 1996.

The trend of decreasing annual births in South Dakota continued with a decline to 10,470 live births in 1995. The state's infant mortality rate (IMR) of 9.5 per 1,000 live births for 1995 decreased from 9.6 in 1994, but has essentially varied little over the past nine years and is currently higher than the nation's rate of 7.5. Neonatal mortality (zero to 27 days of life) in South Dakota decreased to 5.2 in 1995 from 5.5 in 1994 with the decline attributable to fewer deaths of newborns of color. Nonetheless, similar to 1994 this rate is higher than the provisional national 1995 rate of 4.8. Post neonatal mortality in the state increased in 1995 among both whites and infants of color. An examination of causes of infant deaths in South Dakota shows that the state's rates of infant deaths due to congenital anomalies and Sudden Infant Death Syndrome (SIDS) exceed those noted nationally. The US Public Health Service's "Back to Sleep" campaign, initiated in 1994, is described as a contributor to the recent declining national rate of SIDS and its acceptance is urged as a preventive measure to decrease tragic loss of new life in South Dakota.

Birth Rate↗