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Biomedical subjects

K Fitzgerald

Publications and source records attributed to K Fitzgerald.

At least 19 recordsLinked to original sources
PubMed2003

Lessons for increasing awareness and use of booster seats in a Latino community.

OBJECTIVES: Latino children are more likely to be unrestrained passengers in motor vehicles than non-Latino children, but little is known about the use of booster seats in Latino families. This study investigates Latino parents' knowledge, attitudes and beliefs about booster seats, barriers to booster seat use, and effective strategies for message delivery in the Latino community. METHODS: Two focus groups were conducted with Spanish speaking parents. Information was obtained through a written survey and moderated discussions. RESULTS: Parents were widely misinformed about recommended guidelines for booster seat use, and the majority of participants did not own a booster seat. Parents identified a lack of information, the cost of booster seats, resistance to use by the child or the father, limited space in the vehicle, and unavailability of shoulder belts as barriers to booster seat use. Participants felt that learning more about the new Washington state booster seat law and its consequences would increase booster seat use. Public health messages felt to be effective were those in Spanish, delivered by credible spokespeople such as physicians and teachers, and utilizing the Spanish media. CONCLUSIONS: Campaigns to promote booster seats in the Latino community should be culturally specific, and clear guidelines for booster seat use should be given in Spanish. Legislation may be an important incentive for using booster seats, though reducing their cost and providing strategies to address child resistance and physical constraints of some vehicles are also important.

Attitude to Health↗
PubMed2001

The small GTPase Rab4A interacts with the central region of cytoplasmic dynein light intermediate chain-1.

Rab4 belongs to the Rab family of small GTPases involved in the regulation of intracellular transport, and has been localized to early endosomes. We have employed the yeast two-hybrid system to identify proteins that specifically interact with Rab4AQ67L, a GTPase-deficient mutant form of Rab4A. Screening a mouse embryo cDNA library identified a clone (M449) that interacted with Rab4A in a nucleotide-dependent fashion. Data base searches identified this clone as the mouse cytoplasmic dynein light intermediate chain-1 (LIC-1). Based on this finding, the full-length equivalent human cytoplasmic dynein LIC-1 was isolated by PCR. When Rab4A was overexpressed together with either M449 or dynein LIC-1 in HeLa cells, the proteins were found to colocalize in the perinuclear region. We characterize the localization of both overexpressed human dynein LIC-1 and the endogenous protein with respect to microtubules and show that it concentrates to the microtubule-organizing center and mitotic spindle. Additionally, GFPRab4A endosomes localize to microtubules and are redistributed by nocodazole treatment. This is the first described interaction between cytoplasmic dynein, a retrograde motor protein, and a Rab protein.

Amino Acid Sequence↗
PubMed2001

Isolation of a murine homologue of the Drosophila neuralized gene, a gene required for axonemal integrity in spermatozoa and terminal maturation of the mammary gland.

The Drosophila neuralized gene shows genetic interactions with Notch, Enhancer of split, and other neurogenic genes and is thought to be involved in cell fate specification in the central nervous system and the mesoderm. In addition, a human homologue of the Drosophila neuralized gene has been described as a potential tumor suppressor gene in malignant astrocytomas. We have isolated a murine homologue of the Drosophila and human Neuralized genes and, in an effort to understand its physiological function, derived mice with a targeted deletion of this gene. Surprisingly, mice homozygous for the introduced mutation do not show aberrant cell fate specifications in the central nervous system or in the developing mesoderm. This is in contrast to mice with targeted deletions in other vertebrate homologues of neurogenic genes such as Notch, Delta, and Cbf-1. Male Neuralized null mice, however, are sterile due to a defect in axoneme organization in the spermatozoa that leads to highly compromised tail movement and sperm immotility. In addition, female Neuralized null animals are defective in the final stages of mammary gland maturation during pregnancy.

Amino Acid Sequence↗
PubMed2001

Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial.

OBJECTIVES: A randomized, masked, controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids, arachidonic acid (AA; 20:4 n6), and docosahexaenoic acid (DHA; 22:6 n3) on growth, visual acuity, and multiple indices of development. METHODS: Infants (N = 470) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids: 1) control (N = 144), 2) AA+DHA from fish/fungal oil (N = 140), and 3) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil (N = 143). Infants were fed human milk and/or Similac Special Care with or without 0.42% AA and 0.26% DHA to term corrected age (CA), then fed human milk or NeoSure with or without 0.42% AA and 0.16% DHA to 12 months' CA. Infants fed exclusively human milk to term CA (EHM-T; N = 43) served as a reference. RESULTS: Visual acuity measured by acuity cards at 2, 4, and 6 months' CA was not different among groups. Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites (45 control, 50 AA+DHA [fish/fungal]; 39 AA+DHA [egg-TG/fish]; and 23 EHM-T) was better in both the AA+DHA (fish/fungal; least square [LS] means [cycle/degree] +/- standard error [SE; octaves] 11.4 +/- 0.1) and AA+DHA (egg-TG/fish; 12.5 +/- 0.1) than control (8.4 +/- 0.1) and closer to that of the EHM-T group (16.0 +/- 0.2) at 6 months' CA. Visual acuity improved from 4 to 6 months' CA in all but the control group. Scores on the Fagan test of novelty preference were greater in AA+DHA (egg-TG/fish; LS means +/- SE, 59.4 +/- 7.7) than AA+DHA (fish/fungal; 57.0 +/- 7.5) and control (57.5 +/- 7.4) at 6 months' CA, but not at 9 months' CA. There were no differences in the Bayley Mental Development Index at 12 months' CA. However, the Bayley motor development index was higher for AA+DHA (fish/fungal; LS means +/- SE, 90.6 +/- 4.4) than control (81.8 +/- 4.3) for infants </=1250 g. When Spanish-speaking infants and twins were excluded from the analyses, the MacArthur Communicative Development Inventory revealed that control infants (LS means +/- SE, 94.1 +/- 2.9) had lower vocabulary comprehension at 14 months' CA than AA+DHA (fish/fungal) infants (100.6 +/- 2.9) or AA+DHA (egg-TG/fish) infants (102.2 +/- 2.8). There were no consistent differences in weight, length, head circumference, or anthropometric gains. CONCLUSION: These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months' CA.

Apgar Score↗
PubMed2000

Ras pathway signals are required for notch-mediated oncogenesis.

The Notch genes of C. elegans, Drosophila melanogaster and vertebrates encode receptors responsible for cell fate decisions during development. These Notch receptors and their ligands, Delta and Jagged, have been implicated in several human diseases. Truncated, constitutively active mutant forms of the Notch receptor appear to be involved in human T-cell leukemia, mammary carcinomas in mice, and a tumorous germline phenotype in C. elegans. Since activated Notch induces solitary tumors in transgenic mice, it is highly likely that collaborating genetic events are required for tumor formation. We have assessed four signal transduction pathways to determine which might play additional roles in malignant transformation in concert with activated Notch4. Our results suggest that transformation by Notch does not, as might have been expected, depend on the Src-like kinases Lck and Fyn, nor upon signals from protein kinase A and C (PKA, PKC). Rather, transformation by Notch requires active signals from the Erk/MAP kinase and PI-3 kinase pathways downstream of Ras. Oncogene (2000) 19, 4191 - 4198

Animals↗
PubMed2000

Electroretinography is necessary for spasmus nutans diagnosis.

The purpose of the present study was to determine whether that which clinically appeared to be spasmus nutans could actually represent retinal sensory deficits diagnosable by electroretinography. Eight patients clinically thought to have spasmus nutans underwent electroretinography according to international standards. Five had normal electroretinograms and represented cases of true spasmus nutans. Three patients had abnormal electroretinograms, indicating that they did not have spasmus nutans. The clinical findings used to diagnose spasmus nutans can be simulated by retinal dystrophies. A normal electroretinogram is needed to confirm the diagnosis of spasmus nutans.

Case-Control Studies↗
PubMed1999

Association of compartment defects in pelvic floor dysfunction.

OBJECTIVE: Dynamic cystoproctography was used to determine the frequency of associated urinary, genital, and anorectal abnormalities in women with pelvic floor dysfunction. SUBJECTS AND METHODS: We categorized, by pelvic floor compartments, the symptoms at presentation of 100 consecutive female patients who had been referred for dynamic cystoproctography. We then analyzed the compartment defects seen on dynamic cystoproctography relative to those detected on clinical presentation. RESULTS: Of the 20 patients with symptoms of anterior compartment (urinary) defect, dynamic cystoproctography revealed that 45% had vaginal vault prolapse of more than 50% and that 90% had rectoceles. Of the 45 patients with symptoms of middle compartment (genital) defect, dynamic cystoproctography revealed that 91% had cystoceles, 56% had a hypermobile bladder neck, 82% had rectoceles, 58% had enteroceles, 11% had sigmoidoceles, 20% had rectoanal intussusception, and 16% had anal incontinence. Of the 17 patients with symptoms of posterior compartment (anorectal) defect, dynamic cystoproctography showed that 71% had cystoceles, 65% had a hypermobile bladder neck, and 35% had vaginal vault prolapse of more than 50%. Of the 18 patients with symptoms of defects from a combination of compartments, dynamic cystoproctography revealed that 89% had cystoceles, 56% had a hypermobile bladder neck, 39% had vaginal vault prolapse exceeding 50%, 100% had rectoceles (of which 45% were large), 6% had enteroceles, 6% had sigmoidoceles, 22% had rectoanal intussusception, and 6% had anal incontinence. CONCLUSION: Although patients may present with symptoms that involve only one compartment, a multicompartment prolapse is usually revealed on dynamic cystoproctography. Of the patients with pelvic floor dysfunction, 95% had abnormalities in all three compartments.

Fecal Incontinence↗
PubMed1998

Clinical benchmarking: implications for perinatal nursing.

Health care is a dynamic environment where expectations of quality must be balanced with appropriateness of treatment and cost of care. Managers often have inadequate information on which to base decisions, policy, and practice. Clinical benchmarking is a tool and a process of continuously comparing the practices and performances of one's operations against those of the best in the industry or the focused area of service and then using that information to enhance and improve performance and productivity. The article discusses the advantages and disadvantages of benchmarking as well as the factors influencing the need for such tools in health care and in perinatal nursing.

Benchmarking↗
PubMed1998

GATA-6 stimulates a cell line-specific activation element in the human lactase promoter.

Lactase-phlorizin hydrolase (LPH) synthesis is restricted to differentiated small intestinal enterocytes and is highly regulated during development. Analysis of expression of LPH promoter segments fused with luciferase transfected in Caco-2 cells, a line that uniquely expresses LPH mRNA, mapped an 18-base pair (bp) segment 100 bp upstream of the transcription start site that is required for transactivation. Remarkably, the LPH upstream element (LUE) has no stimulatory activity in both human intestinal and nonintestinal lines in which LPH mRNA is absent. Electrophoretic analysis of sequence-specific DNA-nuclear protein complexes demonstrated the presence of a Caco-2 cell-specific protein(s) (CCP), which is uniformly absent in LPH nonproducer cell lines. Mutational analysis of the LUE demonstrated that bases contained within a GATA consensus motif are critical for both CCP binding and transcription from the LPH promoter. Caco-2 cells express high levels of GATA-6 mRNA in a cell line-specific manner, suggesting that GATA-6 is a CCP that complexes with the LUE. When expressed by a plasmid, GATA-6 transactivated the LPH promoter. The stimulation was abrogated with mutations in the GATA consensus motif as well as mutations in a flanking downstream element. These studies are consistent with an important role of an intestinal GATA binding protein in cell type-specific transactivation of the LPH promoter.

Caco-2 Cells↗
PubMed1997

The safety of ranitidine in over a decade of use.

BACKGROUND: Ranitidine hydrochloride (Zantac) is one of the most extensively studied and widely used drugs of all time. This has provided an excellent opportunity to define its safety profile. METHODS: Data from 189 controlled clinical trials in which more than 26,000 patients received daily doses of ranitidine for 4 weeks or more were reviewed. More than 80% of patients were treated with up to 300 mg ranitidine daily; the remaining patients received doses of up to 1200 mg daily. Eighty-seven trials were placebo controlled. Analyses of post-marketing surveillance and a database of all spontaneously reported adverse events were also evaluated. RESULTS: Overall in the clinical trial programme adverse events were reported by 20% of those receiving ranitidine compared with 27% of those receiving placebo. The pattern of events was similar in all treatment groups with no evidence of dose-related toxicity in regimens encompassing an eightfold range of therapeutic doses. Similarly in a programme of studies designed to evaluate a dose of ranitidine of 75 mg for non-prescription (over-the-counter) use in the treatment of heartburn, ranitidine was not associated with an adverse event profile distinct from that of placebo. Analysis of spontaneously reported adverse event data allowed identification of rare idiosyncratic events. CONCLUSIONS: Review of data from a large population of controlled clinical trials with analyses of postmarketing surveillance studies and spontaneously reported adverse events confirmed the excellent safety profile of ranitidine.

Anti-Ulcer Agents↗
PubMed1995

Parkinson's disease.

Explore the source record for details and available documents.

Antiparkinson Agents↗
PubMed1995

Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo.

Ligands of the Delta/Serrate/lag-2 (DSL) family and their receptors, members of the lin-12/Notch family, mediate cell-cell interactions that specify cell fate in invertebrates and vertebrates. In C. elegans, two DSL genes, lag-2 and apx-1, influence different cell fate decisions during development. Here we show that APX-1 can fully substitute for LAG-2 when expressed under the control of lag-2 regulatory sequences. In addition, we demonstrate that truncated forms lacking the transmembrane and intracellular domains of both LAG-2 and APX-1 can also substitute for endogenous lag-2 activity. Moreover, we provide evidence that these truncated forms are secreted and able to activate LIN-12 and GLP-1 ectopically. Finally, we show that expression of a secreted DSL domain alone may enhance endogenous LAG-2 signalling. Our data suggest ways that activated forms of DSL ligands in other systems may be created.

Animals↗
PubMed1994

Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to commitment in a C. elegans cell fate decision.

During development of the C. elegans hermaphrodite gonad, two cells interact with each other, so that one chooses to become the anchor cell (AC) and the other becomes a ventral uterine precursor cell (VU). This interaction is mediated by the receptor LIN-12 and its apparent ligand LAG-2. We show that initially lin-12 and lag-2 are expressed in both cells, but prior to commitment, the expression patterns change in a reciprocal manner, so that lin-12 expression becomes restricted to the presumptive VU and lag-2 expression becomes restricted to the presumptive AC. In addition, lin-12 activity promotes expression of lin-12 and represses expression of lag-2. Furthermore, we show that positive autoregulation of lin-12 transcription in the presumptive VU is mediated by a cis-acting 5' regulatory sequence and is necessary to specify the VU fate. Our results suggest that transcriptional control is a component of the feedback mechanism involved in specifying the AC and VU fates.

Animals↗
PubMed1993

Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo.

The lin-12 gene of C. elegans and the Notch gene of D. melanogaster encode structurally related transmembrane proteins that mediate intercellular signaling. We show that truncated forms of these proteins consisting of only the intracellular domains cause cell fate transformations associated with constitutive activity in their respective organisms. This activity does not depend on endogenous gene function. Our results indicate that the intracellular domains of Lin-12 and Notch have intrinsic activity and that the principal role of the extracellular domains in the intact proteins is to regulate this activity. Our results also suggest that equivalent truncated forms of lin-12/Notch family members in vertebrates, including known oncogenes, are similarly active.

Anal Canal↗