Biomedical subjects

R L Davis

Publications and source records attributed to R L Davis.

At least 19 recordsLinked to original sources

PubMed2001

Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning.

The basic-helix-loop-helix (bHLH) proteins are a superfamily of DNA-binding transcription factors that regulate numerous biological processes in both invertebrates and vertebrates. One family of bHLH transcriptional repressors is related to the Drosophila hairy and Enhancer-of-split proteins. These repressors contain a tandem arrangement of the bHLH domain and an adjacent sequence known as the Orange domain, so we refer to these proteins as bHLH-Orange or bHLH-O proteins. Phylogenetic analysis reveals the existence of four bHLH-O subfamilies, with distinct, evolutionarily conserved features. A principal function of bHLH-O proteins is to bind to specific DNA sequences and recruit transcriptional corepressors to inhibit target gene expression. However, it is likely that bHLH-O proteins repress transcription by additional mechanisms as well. Many vertebrate bHLH-O proteins are effectors of the Notch signaling pathway, and bHLH-O proteins are involved in regulating neurogenesis, vasculogenesis, mesoderm segmentation, myogenesis, and T lymphocyte development. In this review, we discuss mechanisms of action and biological roles for the vertebrate bHLH-O proteins, as well as some of the unresolved questions about the functions and regulation of these proteins during development and in human disease.

Amino Acid Sequence↗

PubMed2001

Presenilin-1 and memories of the forebrain.

In this issue of Neuron, report that forebrain-specific Presenilin-1 conditional knockout mice show defects in enrichment-induced neurogenesis in the dentate gyrus. This defect in neurogenesis is associated with enhanced fear memory of contextual cues when animals are subjected to enrichment between training and testing. The authors suggest that neurogenesis in the adult dentate gyrus may serve to clear out old memory traces from the hippocampus, thus leaving the hippocampus available for new memory processing.

Alzheimer Disease↗

PubMed2001

P[Switch], a system for spatial and temporal control of gene expression in Drosophila melanogaster.

We have developed a method for turning on and off the expression of transgenes within Drosophila in both time and space. Two different enhancer detector elements carrying an RU486-inducible form of the yeast transcription factor GAL4 were constructed and used to generate enhancer detector lines. These lines were screened for RU486-inducible reporter gene expression in the adult head. We identified lines that exhibit inducible expression in many cell and tissue types, verifying that the elements respond to nearby enhancers. No expression was detected in the absence of the ligand. The P[Switch1] element responded to genomic enhancers less efficiently than P[Switch2] but produced more specific patterns of expression. Two P[Switch] lines were used to ablate fat body tissue in adult females through the induced expression of diphtheria toxin. These females were sterile, which correlates with fat body loss, and they died prematurely.

Animals↗

PubMed2001

The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine.

BACKGROUND: The administration of the diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccine and measles, mumps, and rubella (MMR) vaccine has been associated with adverse neurologic events, including seizures. We studied the relation between these vaccinations and the risk of a first seizure, subsequent seizures, and neurodevelopmental disability in children. METHODS: This cohort study was conducted at four large health maintenance organizations and included reviews of the medical records of children with seizures. We calculated the relative risks of febrile and nonfebrile seizures among 679,942 children after 340,386 vaccinations with DTP vaccine, 137,457 vaccinations with MMR vaccine, or no recent vaccination. Children who had febrile seizures after vaccination were followed to identify the risk of subsequent seizures and other neurologic disabilities. RESULTS: Receipt of DTP vaccine was associated with an increased risk of febrile seizures only on the day of vaccination (adjusted relative risk, 5.70; 95 percent confidence interval, 1.98 to 16.42). Receipt of MMR vaccine was associated with an increased risk of febrile seizures 8 to 14 days after vaccination (relative risk, 2.83; 95 percent confidence interval, 1.44 to 5.55). Neither vaccination was associated with an increased risk of nonfebrile seizures. Analyses of automated data alone gave results similar to the analyses of the data from medical-record reviews. The number of febrile seizures attributable to the administration of DTP and MMR vaccines was estimated to be 6 to 9 and 25 to 34 per 100,000 children, respectively. As compared with other children with febrile seizures that were not associated with vaccination, the children who had febrile seizures after vaccination were not found to be at higher risk for subsequent seizures or neurodevelopmental disabilities. CONCLUSIONS: There are significantly elevated risks of febrile seizures on the day of receipt of DTP vaccine and 8 to 14 days after the receipt of MMR vaccine, but these risks do not appear to be associated with any long-term, adverse consequences.

Child↗

PubMed2001

Drosophila fasciclinII is required for the formation of odor memories and for normal sensitivity to alcohol.

Drosophila fasciclinII (fasII) mutants perform poorly after olfactory conditioning due to a defect in encoding, stabilizing, or retrieving short-term memories. Performance was rescued by inducing the expression of a normal transgene just before training and immediate testing. Induction after training but before testing failed to rescue performance, showing that Fas II does not have an exclusive role in memory retrieval processes. The stability of odor memories in fasII mutants are indistinguishable from control animals when initial performance is normalized. Like several other mutants deficient in odor learning, fasII mutants exhibit a heightened sensitivity to ethanol vapors. A combination of behavioral and genetic strategies have therefore revealed a role for Fas II in the molecular operations of encoding short-term odor memories and conferring alcohol sensitivity. The preferential expression of Fas II in the axons of mushroom body neurons furthermore suggests that short-term odor memories are formed in these neurites.

Animals↗

PubMed2001

The role of Drosophila mushroom body signaling in olfactory memory.

The mushroom bodies of the Drosophila brain are important for olfactory learning and memory. To investigate the requirement for mushroom body signaling during the different phases of memory processing, we transiently inactivated neurotransmission through this region of the brain by expressing a temperature-sensitive allele of the shibire dynamin guanosine triphosphatase, which is required for synaptic transmission. Inactivation of mushroom body signaling through alpha/beta neurons during different phases of memory processing revealed a requirement for mushroom body signaling during memory retrieval, but not during acquisition or consolidation.

Afferent Pathways↗

PubMed2001

Ethnicity delineates different genetic pathways in malignant glioma.

In the United States and the San Francisco Bay Area, whites are nearly twice as likely as non-whites to develop brain cancer. To test whether prevalence and types of alterations in the p53 pathway in brain tumor development may explain some of this difference in risk, we have analyzed the p53 status of astrocytic gliomas from a population-based sample of cases within our San Francisco Bay Area Adult Glioma Study. We identified mutations in exons 5-8 of p53 using DNA extracted from formalin-fixed paraffin-embedded tissue blocks from 146 whites and 26 non-whites with astrocytic glioma by PCR-single-strand conformation polymorphism and direct sequencing. Tumor P53 protein (TP53) immunohistochemistry (IHC) available for 164 of these cases showed that tumors from 50% (13 of 26) of non-whites and 32% (44 of 138) of whites contained intense IHC staining for TP53, indicating persistence of TP53 protein. Irrespective of IHC status, tumors from 42% (11 of 26) of non-whites versus 13% (19 of 146) of whites contained p53 mutations (age/gender-adjusted odds ratio, 5.7; 95% confidence interval, 2.2-15.1; P = 0.0004). Patients with p53 mutation-positive tumors were also significantly younger than patients with mutation-negative tumors and somewhat more likely to be female. A higher proportion of tumors from non-whites than from whites had transition mutations, but there were similar proportions of transversion mutations in tumors from whites and non-whites. Whites and non-whites also had similar proportions of tumors with p53 mutations that stained intensely for TP53 (78 and 82%, respectively). Because whites have higher risk for glioma than non-whites in this population, that the gliomas from whites were less likely than those from non-whites to have p53 mutation suggests that whites may be more likely than non-whites to be at risk for the more common type of astrocytic gliomas, which do not contain p53 mutations.

Adult↗

PubMed2001

Comparative efficacy of several insecticides for control of cattle lice (Mallophaga: Trichodectidae and Anoplura: Haematopinidae).

Several insecticides were applied to cattle at various rates, mixtures, application methods and numbers of treatments and evaluated for control of cattle lice. The insecticides included permethrin at various rates as a pour-on with and without the synergist piperonyl butoxide (PBO), and also at various rates as a spray with and without PBO. Pirimiphos-methyl was evaluated as a pour-on at various rates and with one or two applications. Lambda cyhalothrin in microencapsulated formulation was compared to a non-microencapsulated formulation. Rabon(R) was applied as a pour-on at two rates and at one or two treatments for each rate. Dimilin(R) was applied as a pour-on at two rates and mixed with permethrin and applied at two rates. Five endectocides, Eprinex(R), Ivomec(R), Dectomax(R), Cydectin(R) and Phoenectin(R) were all applied at the same rate. The cattle utilized in this research were all infested with a mixture of lice species. The species included: Bovicola (Damalinia) bovis (L.), Haematopinus eurysternus (Nitzsch), Linognthus vituli (L.) and Solenoptes capillatus (Enderlein). Most of the cattle were infested with at least two species and some had three or all four species present. All of the treatments except permethrin 1.0%+5% PBO, at a rate of 3ml/45.4kgwt. provided acceptable lice control with one application. Data indicated that applying the insecticides in early January should provide enough control to render the need for a second treatment unnecessary.

Animals↗

PubMed2001

Phase III trial of accelerated hyperfractionation with or without difluromethylornithine (DFMO) versus standard fractionated radiotherapy with or without DFMO for newly diagnosed patients with glioblastoma multiforme.

PURPOSE: To report the results of a prospective Phase III trial for patients with newly diagnosed glioblastoma multiforme (GBM), treated with either accelerated hyperfractionated irradiation with or without difluromethylornithine (DFMO) or standard fractionated irradiation with or without DFMO. METHODS AND MATERIALS: Adult patients with newly diagnosed GBM were registered and randomized following surgery to one of 4 treatment arms: Arm A, accelerated hyperfractionation alone using 2 fractions a day of 1.6 Gy to a total dose of 70.4 Gy in 44 fractions; Arm B, accelerated hyperfractionation as above plus DFMO 1.8 gm/m2 by mouth every 8 h beginning one week before radiation until the last fraction was given; Arm C, single-fraction irradiation of 1.8 Gy/day to 59.4 Gy; Arm D, single-fraction irradiation as in Arm C plus DFMO given as in Arm B. Patients were followed for progression-free survival (PFS) and overall survival (OS), as well as for toxicity. Eligibility required histologically proven GBM, age > or =18, Karnofsky performance status (KPS) > or =60, and no prior chemotherapy or radiotherapy. Adjuvant chemotherapy was not used in this protocol. RESULTS: A total of 231 eligible patients were enrolled. There were 95 men and 136 women with a median age of 57 years, and median KPS of 90. Extent of resection was total in 23, subtotal in 152, and biopsy only in 56 patients. The 4 arms were balanced with respect to age, KPS, and extent of resection. Times to event measurements are from date of diagnosis. Median OS and PFS were 40 and 19 weeks for Arm A; 42 and 22 weeks for Arm B; 37 and 16 weeks for Arm C; and 44 and 19 weeks for Arm D (p = 0.48 for survival; p = 0.32 for PFS). Comparison of the 2 arms treated with DFMO to the 2 arms without DFMO revealed no difference in OS (37 weeks vs. 42 weeks, p = 0.12) or PFS and thus no benefit to the use of DFMO. Comparison of the 2 standard fractionation arms to the 2 accelerated hyperfractionation arms also resulted in no difference in OS (42 weeks vs. 41 weeks, p = 0.75) or PFS, showing no benefit to accelerated hyperfractionated irradiation. CONCLUSION: In this prospective Phase III study, no survival or PFS benefit was seen with accelerated hyperfractionated irradiation to 70.4 Gy, nor was any benefit seen with DFMO as a radiosensitizer. Standard fractionated irradiation to 59.4 Gy remains the treatment of choice for newly diagnosed patients with glioblastoma multiforme.

Adult↗

PubMed2001

Cognitive deficits associated with a recently reported familial neurodegenerative disease: familial encephalopathy with neuroserpin inclusion bodies.

BACKGROUND: We recently discovered an autosomal dominant disease causing a progressive dementia. The disease is caused by a point mutation in the gene coding for the serine protease inhibitor (ie, serpin) neuroserpin. The mutation results in an unstable neuroserpin protein that readily aggregates into intraneuronal inclusions that we identify as Collins bodies. The bodies are distributed throughout the cerebral hemispheres but are significantly more numerous in the cortex and the substantia nigra. We have named the disease familial encephalopathy with neuroserpin inclusion bodies (FENIB). OBJECTIVES: To describe the cognitive and neurophysiological changes exhibited by individuals with FENIB and to correlate the phenotypic expression of the disease with the neuropathological findings. DESIGN: Multiple case studies using neuropsychological assessment, electroencephalography (EEG), magnetic resonance imaging (MRI), and single-photon emission computed tomographic (SPECT) studies of family members were performed. Using these measures, we also compared family members in whom the mutation is present with family members in whom the mutation was absent to control for nonspecific familial factors. SUBJECTS: Nine individuals (5 women, aged 31-64 years; 4 men, aged 43-67 years) from 2 generations of family members related to the first reliably identified individual with symptoms of this disease. Symptoms, by self-report and reports of other family members, ranged from asymptomatic to severe dementia. Six of the 9 individuals carried the disease mutation. RESULTS: All subjects with the mutation demonstrated some cognitive changes, with the greatest demonstrated by subjects older than 40 years. The changes included restricted attention, concentration, and response regulation functions, reduced controlled oral fluency (word-list generation), and restricted visuospatial organization. In general, recall memory was not as affected as other cognitive domains. The most severely affected subject demonstrated global dementia with prominent frontal lobe features. Findings on SPECT showed anomalies limited to frontal areas in the less affected subjects and more global, patchy areas of hypoperfusion in the more severely affected subjects. The 3 oldest and most affected subjects demonstrated slowing on EEG findings. The MRI findings were noncontributory except in the 2 most severe cases, which showed global cortical atrophy. CONCLUSIONS: Cognitive changes in mildly to moderately affected subjects were characterized by deficits in frontal and frontal-subcortical area-dependent processes. Continued progressive deterioration of cerebral functions with relative sparing of recall memory suggests a unique dementia associated with this disease.

Adult↗

PubMed2001

Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease: a case-control study from the Vaccine Safety Datalink project.

CONTEXT: A link between measles virus-containing vaccines and inflammatory bowel disease (IBD) has been suggested by recent studies. OBJECTIVE: To address whether receipt or timing of measles-containing vaccine (MCV) increases risk for IBD. DESIGN: A case-control study. SETTING: Four large health maintenance organizations (HMOs) that are part of the Centers for Disease Control and Prevention's Vaccine Safety Datalink project. PATIENTS OR OTHER PARTICIPANTS: A total of 155 persons with codes from International Classification of Diseases, Ninth Revision specific for IBD, born between 1958 and 1989 and enrolled from birth to the onset of disease, were identified. Up to 5 controls were matched by sex, HMO, and birth year. INTERVENTION: None. MAIN OUTCOME MEASURES: Risk for IBD, Crohn's disease, and ulcerative colitis. RESULTS: Past vaccination was not associated with an increased risk for Crohn's disease (odds ratio [OR] for measles-mumps-rubella vaccine [MMR], 0.4; 95% confidence interval [CI], 0.08-2.0), ulcerative colitis (OR, 0.8; 95% CI, 0.18-3.56), or IBD (OR, 0.59; 95% CI, 0.21-1.68). Risk for IBD was not increased among children vaccinated who were younger than 12 months (OR for MMR, 0.61; 95% CI, 0.15-2.45) or aged 12 to 18 months (OR, 0.86; 95% CI, 0.28-2.59) relative to unvaccinated children. Children vaccinated with MMR who were older than 18 months were at significantly decreased risk for IBD (OR, 0.16; 95% CI, 0.04-0.68). Neither past vaccination nor age at vaccination with other MCV was associated with increased risk for Crohn's disease, ulcerative colitis, or IBD. Risk for Crohn's disease, ulcerative colitis, or IBD was not elevated in the time immediately following vaccination with either vaccine. CONCLUSIONS: Vaccination with MMR or other MCV, or the timing of vaccination early in life, did not increase the risk for IBD.

Adolescent↗

PubMed2001

The rotavirus vaccine's withdrawal and physicians' trust in vaccine safety mechanisms.

OBJECTIVE: To determine how the withdrawal from the market of the rotavirus vaccine has affected physicians' trust in vaccine safety mechanisms, future adherence to vaccine recommendations, and willingness to use a new rotavirus vaccine. DESIGN: National survey mailed to 1228 randomly selected pediatricians and family physicians. MAIN OUTCOME MEASURES: Confidence in vaccine safety mechanisms was defined by agreement with the statements that the system for determining vaccine safety before a vaccine is licensed works well and that the system for monitoring vaccine safety after vaccine licensure works well. Physicians who indicated that they would use a new rotavirus vaccine within 1 year of licensure and recommendation by professional organizations were classified as "early adopters." Logistic regression was used to assess the relationship between trust in vaccine safety mechanisms and future early adoption of new rotavirus vaccines. RESULTS: Following the withdrawal of the rotavirus vaccine, 83% of respondents believed the postlicensure surveillance system works well to monitor vaccine safety, while 22% of respondents believed the prelicensure system works well to determine vaccine safety. After adjusting for physician specialty and years in practice, respondents who believed the prelicensure vaccine safety system works well were significantly more likely to be early adopters than those with less confidence in prelicensure studies (adjusted odds ratio, 2.2 [95% confidence interval, 1.3-3.6]). CONCLUSIONS: Physicians have different levels of trust in prelicensure studies that determine vaccine safety and postlicensure surveillance systems that monitor vaccine safety. Trust in prelicensure vaccine safety evaluations may be associated with early adherence to new vaccine recommendations.

Adverse Drug Reaction Reporting Systems↗

PubMed2001

Molecular biology and anatomy of Drosophila olfactory associative learning.

Most of our current knowledge of olfactory associative learning in Drosophila comes from the behavioral and molecular analysis of mutants that fail to learn. The identities of the genes affected in these mutants implicate new signaling pathways as mediators of associative learning. The expression patterns of these genes provide insight into the neuroanatomical areas that underlie learning. In recent years, there have been great strides in understanding the molecular and neuroanatomical basis for olfaction in insects. It is now clear that much of the association between the conditioned stimuli and the unconditioned stimuli in olfactory learning occurs within mushroom bodies - third order olfactory neurons within the central brain. In this review, we discuss the nature of the behavioral tasks, the molecules, and the neuronal circuits involved in olfactory learning in Drosophila.

Animals↗

PubMed2001

Mushroom bodies, Ca(2+) oscillations, and the memory gene amnesiac.

The memory of odors in Drosophila is mediated by mushroom body neurons. Memory is formed, in part, by a modulation of the physiology of these neurons brought about by neuropeptides that are encoded by the amnesiac gene and released from peptidergic neurons that innervate mushroom body neurons. Slow and spontaneous oscillations of calcium levels are elevated in the mushroom body neurons of amnesiac mutants and may contribute to memory consolidation.

Animals↗

PubMed2001

Molecular targets of vertebrate segmentation: two mechanisms control segmental expression of Xenopus hairy2 during somite formation.

Vertebrate hairy genes are expressed in patterns thought to be readouts of a "segmentation clock" in the presomitic mesoderm. Here we use transgenic Xenopus embryos to show that two types of regulatory elements are required to reconstitute the segmental pattern of Xenopus hairy2. The first is a promoter element containing two binding sites for Xenopus Su(H), a transcriptional activator of Notch target genes. The second is a short sequence in the hairy2 3' untranslated region (UTR), which most likely functions posttranscriptionally to modulate hairy2 RNA levels. 3' UTRs of other hairy-related, segmentally expressed genes can substitute for that of hairy2. Our results demonstrate a novel mechanism regulating the segmental patterns of Notch target genes and suggest that vertebrate segmentation requires the intersection of two regulatory pathways.

3' Untranslated Regions↗

PubMed2001

Introduction of the new Centers for Disease Control and Prevention group B streptococcal prevention guideline at a large West Coast health maintenance organization.

OBJECTIVE: Our purpose was to assess the impact of new consensus guidelines issued by the Centers for Disease Control and Prevention, The American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics to prevent perinatal group B streptococcal disease. STUDY DESIGN: We performed a descriptive analysis and a before-and-after analysis of implementation of the group B streptococcal disease prevention guidelines among singleton-birth pregnancies in 2 Group Health Cooperative hospitals from October 1, 1995, through December 31, 1997. We studied the speed and completeness of implementation and the effect on pregnancy care practices including intrapartum antibiotic use, test ordering, and maternal and neonatal health. RESULTS: Guideline implementation occurred rapidly. The proportion of term pregnancies screened according to the guideline increased markedly, and overall intrapartum antibiotic use more than doubled. Among group B streptococci-positive women, intrapartum antibiotic prophylaxis increased from 24% before to 74% after guideline implementation. Median duration of treatment before delivery increased from 1.8 to 4.3 hours. The rate of rash did not increase, and there were no cases of anaphylaxis or pseudomembranous colitis. The proportion of infants undergoing evaluation decreased after implementation of the neonatal guidelines; among infants of group B streptococci-negative women, test ordering dropped by almost 40%. CONCLUSIONS: Implementation of the new guidelines is feasible and can be accomplished rapidly. The guidelines were associated with increased maternal intrapartum antibiotic use, particularly among women at highest risk, and with a decrease in laboratory use for infants.

Adult↗

PubMed2001

Does influenza vaccination prevent asthma exacerbations in children?

OBJECTIVE: Influenza can exacerbate asthma, particularly in children. The effectiveness of influenza vaccine in preventing influenza-related asthma exacerbations, however, is not known. We evaluated influenza vaccine effectiveness in protecting children against influenza-related asthma exacerbations. STUDY DESIGN: We conducted a population-based retrospective cohort study with medical and vaccination records in 4 large health maintenance organizations in the United States during the 1993-1994, 1994-1995, and 1995-1996 influenza seasons. We studied children with asthma who were 1 through 6 years of age and who were identified by search of computerized databases of medical encounters and pharmacy dispensings. Main outcome measures were exacerbations of asthma evaluated in the emergency department or hospital. RESULTS: Unadjusted rates of asthma exacerbations were higher after influenza vaccination than before vaccination. After adjustment was done for asthma severity by means of a self-control method, however, the incidence rate ratios of asthma exacerbations after vaccination were 0.78 (95% CI: 0.55 to 1.10), 0.59 (0.43 to 0.81), and 0.65 (0.52 to 0.80) compared with the period before vaccination during the 3 influenza seasons. CONCLUSIONS: After controlling for asthma severity, we found that influenza vaccination protects against acute asthma exacerbations in children.

Acute Disease↗

PubMed2001

A randomized controlled trial of point-of-care evidence to improve the antibiotic prescribing practices for otitis media in children.

CONTEXT: Prescribing practices for otitis media are not consistent with current evidence-based recommendations. OBJECTIVE: To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written. DESIGN: Randomized, controlled trial. SETTING: Primary care pediatric clinic affiliated with university training program. Intervention. A point-of-care evidence-based message system presenting real time evidence to providers based on their prescribing practice for otitis media. MAIN OUTCOME MEASURES: Proportion of prescriptions for otitis media that were for <10 days and frequency with which antibiotics were prescribed. RESULTS: Intervention providers had a 34% greater reduction in the proportion of time they prescribed antibiotics for <10 days. Intervention providers were less likely to prescribe antibiotics than were control providers. CONCLUSIONS: A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition.

Adult↗