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Biomedical subjects

R L Davis

Publications and source records attributed to R L Davis.

At least 55 records · Page 3Linked to original sources
PubMed2000

Influenza and the rates of hospitalization for respiratory disease among infants and young children.

BACKGROUND: Young children may be at increased risk for serious complications from influenzavirus infection. However, in population-based studies it has been difficult to separate the effects of influenzavirus from those of respiratory syncytial virus. Respiratory syncytial virus often circulates with influenzaviruses and is the most frequent cause of hospitalization for lower respiratory tract infections in infants and young children. We studied the rates of hospitalization for acute respiratory-disease among infants and children during periods when the circulation of influenzaviruses predominated over the circulation of respiratory syncytial virus. METHODS: For each season from October to May during the period from 1992 to 1997, we used local viral surveillance data to define periods in Washington State and northern California when the circulation of influenzaviruses predominated over that of respiratory syncytial virus. We calculated the rates of hospitalization for acute respiratory disease, excess rates attributable to influenzavirus, and incidence-rate ratios for all infants and children younger than 18 years of age who were enrolled in either the Kaiser Permanente Medical Care Program of Northern California or the Group Health Cooperative of Puget Sound. RESULTS: The rates of hospitalization for acute respiratory disease among children who did not have conditions that put them at high risk for complications of influenza (e.g., asthma, cardiovascular diseases, or premature birth) and who were younger than two years of age were 231 per 100,000 person-months at Northern California Kaiser sites (from 1993 to 1997) and 193 per 100,000 person-months at Group Health Cooperative sites (from 1992 to 1997). These rates were approximately 12 times as high as the rates among children without high-risk conditions who were 5 to 17 years of age (19 per 100,000 person-months at Northern California Kaiser sites and 16 per 100,000 person-months at Group Health Cooperative sites) and approached the rates among children with chronic health conditions who were 5 to 17 years of age (386 per 100,000 person-months and 216 per 100,000 person-months, respectively). CONCLUSIONS: Infants and young children without chronic or serious medical conditions are at increased risk for hospitalization during influenza seasons. Routine influenza vaccination should be considered in these children.

Acute Disease↗
PubMed2000

Does influenza vaccination exacerbate asthma? Analysis of a large cohort of children with asthma. Vaccine Safety Datalink Team.

CONTEXT: Although influenza vaccination is recommended for children with asthma, only a minority are vaccinated. One reason for low influenza vaccine coverage among children with asthma may be concern that influenza vaccination may induce an exacerbation of asthma. OBJECTIVE: To evaluate the safety of influenza vaccination in children with asthma, we studied the incidence of hospitalizations and emergency department visits for asthma following influenza vaccination. DESIGN: Retrospective cohort study-analysis of population-based computerized medical and vaccination records. SETTING: : Four large health maintenance organizations on the West Coast of the United States. SUBJECTS: Children with asthma 1 through 6 years of age, identified by search of computerized databases of medical encounters and pharmacy prescriptions. MAIN OUTCOME MEASURES: Exacerbations of asthma. RESULTS: In unadjusted analyses vaccination was associated with high rates of asthma exacerbations. However, after adjusting for asthma severity using a self-control method, the incidence rate ratios of asthma exacerbations after vaccination were 0.58 (95% confidence interval, 0.36-0.95), 0.74 (95% confidence interval, 0.47-1.17), and 0.98 (95% confidence interval, 0.76-1.27) during the 3 influenza seasons. CONCLUSIONS: After controlling for asthma severity, we found that influenza vaccination does not result in acute asthma exacerbations in children. Concern about possible exacerbation of asthma is not a valid reason to not vaccinate children with asthma against influenza.

Asthma↗
PubMed2000

Antimicrobial use in defined populations of infants and young children.

BACKGROUND: Antimicrobial overprescribing contributes to bacterial resistance, but data on use in infants and young children are limited. OBJECTIVES: To assess antimicrobial use in a defined population of infants and young children and to determine diagnosis-specific prescribing rates for common infections. DESIGN AND SETTING: Retrospective cohort study of children served by 44 practices affiliated with 2 managed care organizations. PATIENTS: Children aged 3 months to 72 months enrolled in either health plan between September 1, 1994, and August 31, 1996. ANALYSIS: Rates of antimicrobial use were calculated as the number of pharmacy dispensings divided by the number of person-years of observation contributed to the cohort in 2 age groups (3 to <36 months and 36 to <72 months). Other outcomes included the distribution of diagnoses associated with antimicrobial dispensing and population-based rates of diagnosis of common acute respiratory tract illnesses. RESULTS: A total of 46477 children contributed 59710 person-years of observation across the 2 health plans. Rates of antimicrobial dispensing for children aged 3 to 36 months were 3.2 and 2.1 dispensings per person-year in the 2 populations. A substantial fraction of younger children (35% in population A and 23% in population B) received 4 or more antimicrobial prescriptions in a single year. For children aged 36 to 72 months, the dispensing rates for the 2 populations were 2.0 and 1.5 antimicrobials per person-year. We found significant differences in rates between the populations studied and a decrease in use at all sites from 1995 to 1996. The diagnosis of otitis media accounted for 56% of antimicrobial drugs dispensed to children aged 3 to 36 months and 40% of those dispensed to children aged 36 to 72 months. Antimicrobial prescribing for colds and upper respiratory tract infections, bronchitis, and sinusitis was less frequent than previously reported but accounted for 10% to 14% of antimicrobial drugs dispensed. CONCLUSIONS: In these populations, otitis media accounted for the largest number of antimicrobial agents dispensed to children younger than 6 years. Clearly inappropriate indications such as cold, upper respiratory tract infection, and bronchitis accounted for smaller fractions of antimicrobial use but may be most amenable to change. However, interventions that encourage use of strict criteria for diagnosis and treatment of otitis media will likely have the greatest impact on overall antimicrobial exposure. Monitoring defined populations longitudinally will allow assessment of the effectiveness of such national and local initiatives.

Anti-Bacterial Agents↗
PubMed2000

DNA guanine-guanine crosslinking sequence specificity of isophosphoramide mustard, the alkylating metabolite of the clinical antitumor agent ifosfamide.

PURPOSE: The purpose of this investigation was to determine the base sequence specificity of isophosphoramide mustard (IPM), the alkylating metabolite of ifosfamide, by crosslinking of designed DNA oligomers in comparison with the clinical alkylating agents mechlorethamine (ME) (nitrogen mustard) and phosphoramide mustard (PM), the alkylating metabolite of cyclophosphamide. METHODS: IPM, as well as PM and ME were each reacted with three dodecameric duplexes, which were designed to detect interstrand crosslinking between guanines in 5'-GC-3' (I), 5'-GNC-3' (II) or 5'-GNNC-3' (III) sequences (N = A or T). RESULTS: All three agents preferentially react with 5'-GNC-3' target sequences. The 5'-GNNC-3' target sequence is less reactive by a factor of approximately 2.5- to 10-fold, while 5'-GC-3' is of even lower reactivity. CONCLUSION: These results indicate that all three agents show approximately equal preference for reaction with a 5'-GNC-3' target sequence in spite of the fact that IPM yields a 7-atom crosslink, while the other two agents yield 5-atom crosslinks.

Antineoplastic Agents, Alkylating↗
PubMed2000

kurtz, a novel nonvisual arrestin, is an essential neural gene in Drosophila.

The kurtz gene encodes a novel nonvisual arrestin. krz is located at the most-distal end of the chromosome 3R, the third gene in from the telomere. krz is expressed throughout development. During early embryogenesis, krz is expressed ubiquitously and later is localized to the central nervous system, maxillary cirri, and antennal sensory organs. In late third instar larvae, krz message is detected in the fat bodies, the ventral portion of the thoracic-abdominal ganglia, the deuterocerebrum, the eye-antennal imaginal disc, and the wing imaginal disc. The krz(1) mutation contains a P-element insertion within the only intron of this gene and results in a severe reduction of function. Mutations in krz have a broad lethal phase extending from late embryogenesis to the third larval instar. The fat bodies of krz(1) larva precociously dissociate during the midthird instar. krz(1) is a type 1 melanotic tumor gene; the fat body is the primary site of melanotic tumor formation during the third instar. We have functionally rescued these phenotypes with both genomic and cDNA transgenes. Importantly, the expression of a full-length krz cDNA within the CNS rescues the krz(1) lethality. These experiments establish the krz nonvisual arrestin as an essential neural gene in Drosophila.

Animals↗
PubMed2000

Neuroserpin mutation S52R causes neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy.

Mutations in the Neuroserpin gene have been reported to cause familial presenile dementia. We describe a new family in which the S52R Neuroserpin mutation is associated with progressive myoclonus epilepsy in 2 siblings. The proband presented myoclonus and epilepsy at age 24, his brother and mother presented a similar disorder when they were 25. A clinical diagnosis of progressive myoclonus epilepsy was made on the proband and his brother. Skin and liver biopsies did not reveal the presence of cytological alterations in the proband. His neurological status worsened over the subsequent 19 yr during which he became demented and had uncontrollable seizures. He died at 43 yr of age from aspiration pneumonia. Neuropathologically, eosinophilic bodies, which were positive for periodic acid-Schiff and immunoreactive with antibodies against human neuroserpin, were present in the perikarya and cell processes of the neurons. They were found in large numbers in the cerebral cortex and substantia nigra and to a lesser extent, in most subcortical gray areas, spinal cord, and dorsal root ganglia. By electron microscopy, the intracytoplasmic bodies were contained within the membranes of the rough endoplasmic reticulum. Occasionally neuroserpin immunopositivity was seen throughout the cytoplasm, even without the presence of well-defined bodies. Our study characterizes for the first time the neuropathologic phenotype associated with hereditary progressive myoclonus epilepsy caused by the S52R Neuroserpin mutation.

Adult↗
PubMed2000

The incidence of Kawasaki syndrome in West Coast health maintenance organizations.

BACKGROUND: Kawasaki syndrome (KS) causes an acute vasculitis of unknown etiology. It is a leading cause of acquired heart disease of children in Japan and the United States. METHODS: We examined the incidence of KS in a well-defined population group of children < or =6 years of age, using data collected through the Vaccine Safety Datalink (VSD) project. The VSD database contains information on >1 million children enrolled in four West Coast health maintenance organizations (HMOs). RESULTS: During 1993 through 1996 a total of 234 physician-diagnosed KS patients were reported in the 4 HMOs; 152 (65.0%) were boys and 195 (83.3%) were <5 years of age. The incidence of KS among children <5 years of age in the HMOs ranged from 9.0 to 19.1 per 100,000 person years. KS incidence was higher among boys in 3 of the sites. In the 2 sites with the highest number of KS patients, a seasonal occurrence of KS in winter and early spring was observed. Overall 226 (96.6%) of the KS patients were reported to have been hospitalized; hospitalization rates for children <5 years of age ranged from 9.0 to 16.8 per 100,000 person years. CONCLUSIONS: The incidence of KS in the HMOs was similar to that reported in other population-based studies in the United States and higher than estimates for Australia and several European countries.

Age Factors↗
PubMed2000

The retinal determination gene, dachshund, is required for mushroom body cell differentiation.

The dachshund gene of Drosophila encodes a putative transcriptional regulator required for eye and leg development. We show here that dachshund is also required for normal brain development. The mushroom bodies of dachshund mutants exhibit a marked reduction in the number of (&agr;) lobe axons, a disorganization of axons extending into horizontal lobes, and aberrant projections into brain areas normally unoccupied by mushroom body processes. The phenotypes become pronounced during pupariation, suggesting that dachshund function is required during this period. GAL4-mediated expression of dachshund in the mushroom bodies rescues the mushroom body phenotypes. Moreover, dachshund mutant mushroom body clones in an otherwise wild-type brain exhibit the phenotypes, indicating an autonomous role for dachshund. Although eyeless, like dachshund, is preferentially expressed in the mushroom body and is genetically upstream of dachshund for eye development, no interaction of these genes was detected for mushroom body development. Thus, dachshund functions in the developing mushroom body neurons to ensure their proper differentiation.

Animals↗
PubMed2000

The fate of cells in the tailbud of Xenopus laevis.

The vertebrate tailbud and trunk form very similar tissues. It has been a controversial question for decades whether cell determination in the developing tail proceeds as part of early axial development or whether it proceeds by a different mechanism. To examine this question more closely, we have used photoactivation of fluorescence to mark small neighborhoods of cells in the developing tailbud of Xenopus laevis. We show that, in one region of the tailbud, very small groups of adjacent cells can contribute progeny to the neural tube, notochord and somitic muscle, as well as other identified cell types within a single embryo. Groups averaging three adjacent cells at a later stage can contribute progeny with a similar distribution. Our data suggest that the tailbud contains multipotent cells that make very late germ-layer decisions.

Animals↗
PubMed2000

Systemic corticosteroids in infant bronchiolitis: A meta-analysis.

OBJECTIVE: To determine whether corticosteroids are efficacious in treating bronchiolitis in hospitalized infants. METHODS: Online bibliographic databases (Medline, Embase, and Cochrane Clinical Trials Registry) were searched for: 1) bronchiolitis or respiratory syncytial virus, and 2) corticosteroid or glucocorticoid or steroidal antiinflammatory agents or adrenal cortex hormones. Reference lists from all selected articles were also examined. Randomized, placebo-controlled trials of systemic corticosteroids in treatment of infants hospitalized with bronchiolitis were selected by 2 investigators. Of 12 relevant publications identified in the literature search, 6 met the selection criteria and had relevant data available. Investigators independently extracted data for 3 outcomes: length of stay (LOS), duration of symptoms (DOS), and clinical scores. RESULTS: In the pooled analysis, infants who received corticosteroids had a mean LOS or DOS that was.43 days less than those who received the placebo treatment (95% confidence interval: -.81 to -.05 days). The effect size for mean clinical score was -1.60 (95% confidence interval: -1.92 to -1.28), favoring treatment. Secondary analyses of mean LOS or DOS were performed on 5 trials that had clearly identified methods of randomization, 5 trials that measured LOS, and 4 trials that clearly excluded infants with previous wheezing. The estimates of effect were similar to the primary analysis but were not statistically significant. CONCLUSIONS: Combined, published reports of the effect of systemic corticosteroids on the course of bronchiolitis suggest a statistically significant improvement in clinical symptoms, LOS, and DOS.

Anti-Inflammatory Agents↗
PubMed2000

The Vaccine Safety Datalink: immunization research in health maintenance organizations in the USA.

The Vaccine Safety Datalink is a collaborative project involving the National Immunization Program of the Centers for Disease Control and Prevention and several large health maintenance organizations in the USA. The project began in 1990 with the primary purpose of rigorously evaluating concerns about the safety of vaccines. Computerized data on vaccination, medical outcome (e.g. outpatient visits, emergency room visits, hospitalizations, and deaths) and covariates (e.g. birth certificates, census data) are prospectively collected and linked under joint protocol at multiple health maintenance organizations for analysis. Approximately 6 million persons (2% of the population of the USA) are now members of health maintenance organizations participating in the Vaccine Safety Datalink, which has proved to be a valuable resource providing important information on a number of vaccine safety issues. The databases and infrastructure created for the Vaccine Safety Datalink have also provided opportunities to address vaccination coverage, cost-effectiveness and other matters connected with immunization as well as matters outside this field.

Centers for Disease Control and Prevention, U.S.↗
PubMed1999

Larval and pupal development of the mushroom bodies in the honey bee, Apis mellifera.

The mushroom bodies are paired neuropils in the insect brain that act as multimodal sensory integration centers and are involved in learning and memory. Our studies, by using 5-bromo-2-deoxyuridine incorporation and the Feulgen technique, show that immediately before pupation, the brain of the developing honey bee (Apis mellifera) contains approximately 2,000 neuroblasts devoted to the production of the mushroom body intrinsic neurons (Kenyon cells). These neuroblasts are descended from four clusters of 45 or fewer neuroblasts each already present in the newly hatched larva. Subpopulations of Kenyon cells, distinct in cytoarchitecture, position, and immunohistochemical traits, are born at different, but overlapping, periods during the development of the mushroom bodies, with the final complement of these neurons in place by the mid-pupal stage. The mushroom bodies of the adult honey bee have a concentric arrangement of Kenyon cell types, with the outer layers born first and pushed to the periphery by later born neurons that remain nearer the center of proliferation. This concentricity is further reflected in morphologic and immunohistochemical traits of the adult neurons, and is demonstrated clearly by the pattern of expression of Drosophila myocyte enhancer factor 2 (DMEF2)-like immunoreactivity. This is the first comprehensive study of larval and pupal development of the honey bee mushroom bodies. Similarities to patterns of neurogenesis observed in the mushroom bodies of other insects and in the vertebrate cerebral cortex are discussed.

Animals↗
PubMed1999

Crystal structure of Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase with XMP, pyrophosphate, and two Mg(2+) ions bound: insights into the catalytic mechanism.

The crystal structure of the Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-xanthosine 5'-monophosphate (XMP)-pyrophosphate-Mg(2+) ternary complex has been determined at 1. 60 A resolution. This biproduct, post-transition state structure is of a T. gondii HGPRT mutant (Asp150Ala or D150A). The D150A mutant has reduced activity (k(cat) lower by 11-, 296-, and 8.6-fold for hypoxanthine, guanine, and xanthine, respectively) compared to wild-type T. gondii HGPRT. The Michaelis constants for purine bases are altered only slightly, whereas those for alpha-D-5-phosphoribosyl 1-pyrophosphate (PRPP) are lower by approximately 6.5-fold. The ternary complex crystallizes in space group C222(1) (a = 55.21 A, b = 112.25 A, and c = 144.28 A) with two subunits in the asymmetric unit; the HGPRT tetramer is completed by the application of 2-fold crystallographic symmetry. All active sites contain XMP ¿bound in a fashion similar to that of the guanosine 5'-monophosphate (GMP) and inosine 5'-monophosphate (IMP) complexes reported in the preceding article [Héroux, A., et al. (1999) Biochemistry 38, 14485-14494]¿, pyrophosphate, and two Mg(2+) ions. Each Mg(2+) ion is octahedrally coordinated by two terminal pyrophosphate oxygen atoms and several ordered water molecules. This structure shows how HGPRT uses two Mg(2+) ions to orient and activate the pyrophosphate moiety of PRPP for attack by a purine base, and why mutation in humans of the residue corresponding to Asp206, the only HGPRT amino acid that directly contacts the Mg(2+) ions, causes Lesch-Nyhan syndrome (HGPRT(Kinston), D193N). The Leu78-Lys79 peptide bond in the active site adopts the cis configuration, which it must to bind PRPP or pyrophosphate. The contribution of cis-trans isomerization of this peptide bond to the energetics of substrate binding and product release is discussed. A comprehensive description of the HGPRT reaction mechanism is also proposed.

Animals↗
PubMed1999

Familial dementia caused by polymerization of mutant neuroserpin.

Aberrant protein processing with tissue deposition is associated with many common neurodegenerative disorders; however, the complex interplay of genetic and environmental factors has made it difficult to decipher the sequence of events linking protein aggregation with clinical disease. Substantial progress has been made toward understanding the pathophysiology of prototypical conformational diseases and protein polymerization in the superfamily of serine proteinase inhibitors (serpins). Here we describe a new disease, familial encephalopathy with neuroserpin inclusion bodies, characterized clinically as an autosomal dominantly inherited dementia, histologically by unique neuronal inclusion bodies and biochemically by polymers of the neuron-specific serpin, neuroserpin. We report the cosegregation of point mutations in the neuroserpin gene (PI12) with the disease in two families. The significance of one mutation, S49P, is evident from its homology to a previously described serpin mutations, whereas that of the other, S52R, is predicted by modelling of the serpin template. Our findings provide a molecular mechanism for a familial dementia and imply that inhibitors of protein polymerization may be effective therapies for this disorder and perhaps for other more common neurodegenerative diseases.

Biopolymers↗
PubMed1999

Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin.

The multisubunit MSL dosage compensation complex binds to hundreds of sites along the Drosophila single male X chromosome, mediating its hypertranscription. The male X chromosome is also coated with noncoding roX RNAs. When either msl3, mle, or mof is mutant, a partial MSL complex is bound at only approximately 35 unusual sites distributed along the X. We show that two of these sites are the roX1 and roX2 genes and postulate that one of their functions is to provide entry sites for the MSL complex to recognize the X chromosome. The roX1 gene provides a nucleation site for extensive spreading of the MSL complex into flanking chromatin even when moved to an autosome. The spreading can occur in cis or in trans between paired homologs. We present a model for how the dosage compensation complex recognizes X chromatin.

Animals↗
PubMed1999

Immunization levels among premature and low-birth-weight infants and risk factors for delayed up-to-date immunization status. Centers for Disease Control and Prevention Vaccine Safety Datalink Group.

CONTEXT: Studies have noted that health care professionals may not conform to proper immunization schedules for premature and low-birth-weight infants in the United States. Little is known about the success of current efforts to immunize these high-risk infants. OBJECTIVE: To describe current immunization practices for premature and low-birth-weight infants and ascertain risk factors for poor immunization status, using large population-based data sources. DESIGN AND SETTING: Cohort and case-control analyses of immunization data tracked from March 1991 through March 1997 for 3 large health maintenance organizations (HMOs) participating in the Centers for Disease Control and Prevention's Vaccine Safety Datalink project. PARTICIPANTS: A total of 11580 low-birth-weight and premature infants were enrolled from birth to age 2 months; 6832 of these were continuously enrolled from birth to age 24 months. At age 2 months, there were 173373 full-term, normal-birth-weight infants enrolled as controls; at age 24 months, there were 103 324. MAIN OUTCOME MEASURES: Age-specific immunization status by prematurity and birth weight (<1500 g, 1500-2500 g, born at <38 weeks' gestation with birth weight of >2500 g, or full-term with normal birth weight) and patient characteristics associated with up-to-date status. RESULTS: At each age, infants weighing less than 1500 g at birth had lower up-to-date immunization levels than other infants. At age 6 months, 52% to 65% of infants weighing less than 1500 g were up-to-date at each of the 3 HMOs compared with 69% to 73% of those weighing 1500 to 2500 g, 66% to 80% of premature infants weighing more than 2500 g, and 65% to 76% of full-term, normal-birth-weight infants. By age 24 months, 78% to 86% of infants weighing less than 1500 g were up-to-date, significantly less than heavier infants, who had levels of 84% to 89%. Well-child preventive care strongly predicted immunization status, while concomitant pulmonary disease did not. CONCLUSIONS: Our data suggest that infants born prematurely are vaccinated at levels approaching that of the general population, but levels of vaccination for very low-birth-weight infants lag slightly behind.

Health Maintenance Organizations↗