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Biomedical subjects

S Fitzgerald

Publications and source records attributed to S Fitzgerald.

At least 37 records · Page 2Linked to original sources
PubMed1999

Genetic variation in apolipoprotein H (beta2-glycoprotein I) affects the occurrence of antiphospholipid antibodies and apolipoprotein H concentrations in systemic lupus erythematosus.

Apolipoprotein H (apoH, protein; APOH, gene) is a required cofactor for the production of antiphospholipid antibodies (APA). In this study we have examined whether genetic variation in the APOH gene affects variation in risk for systemic lupus erythematosus (SLE), occurrence of antiphospholipid antibodies (APA), anti-apoH, and plasma apoH concentrations. A total of 222 white SLE women were screened for four APOH polymorphisms (codons 88, 247, 306, and 316) by polymerase chain reaction, and for plasma apoH concentrations by ELISA. Of these, 29.3% were positive for APA (APA-positive group) and 31.1% for anti-apoH. None of the four APOH polymorphisms were significantly associated with variation in risk for SLE. The codons 306 and 316 polymorphisms showed significant, gene-dosage effects on plasma apoH concentrations (P<0.0001) and explained 30% and 13%, respectively, of the residual variation in apoH concentrations. No significant association was observed between anti-apoH status and APOH polymorphisms or plasma apoH levels. However, plasma apoH concentrations were significantly higher in patients positive for APA than in patients negative for APA (18.5+/-4.0 mg/dl vs 17.1+/-3. 8 mg/dl; P=0.02). The distribution of the Trp316Ser polymorphism was significantly different between the APA-positive and APA-negative groups. The frequency of the mutant allele (Ser316) was significantly lower in the APA-positive group than the APA-negative group (3.1% vs 12.1% P<0.04), indicating that the Ser316 mutation is protective against the production of phospholipid-apoH dependent APA. Our data indicate that common genetic variation in the APOH gene is a significant determinant of plasma apoH variation in SLE patients, and the Trp316Ser polymorphism appears to provide protection against the production of APA in SLE patients.

Adult↗
PubMed1999

Urinary incontinence in working women: an exploratory study.

Women who work for a large academic center were surveyed about urinary incontinence. The response rate was 57%. Of the 1113 usable questionnaires, 232 (21%) indicated that urinary incontinence occurred at least monthly. The average age of incontinent women was 45 years (SD = 10 years). Incontinent women were significantly older and had a higher body mass index than continent women. There were also ethnic differences between incontinent and continent groups, although ethnicity was not a predictor of incontinence. Only a third of the women thought incontinence was an important problem to resolve and 46% reported incontinence to their physician or nurse. Forty percent reported that they did not know if the incontinence could be improved, but 81% wanted to learn more about incontinence.

Adolescent↗
PubMed1998

Screening high-risk adolescent males for Chlamydia trachomatis infection. Obtaining urine specimens in the field.

BACKGROUND AND OBJECTIVES: Reported case data suggest that few men are being tested for Chlamydia trachomatis (CT) infection (female:male reported case ratio is > 5:1) partially because men seek preventive health services less frequently than women and, until recently, obtaining a CT specimen from men required a urethral swab, which has low patient acceptability. A study was conducted in San Diego, CA, to determine whether urine specimens could be obtained from high-risk teen males in the field using a peer teen outreach approach. GOALS: Identify teen males infected with CT and provide treatment and partner management services. STUDY DESIGN: Prevalence survey of 261 teen males and a program cost evaluation. RESULTS: During the 6.5-month study period (Dec 15, 1995 to June 30, 1996) an estimated 1,860 teen males were approached and 261 submitted a urine specimen; 16 (6.1%) were positive by polymerase chain reaction. All positive males were treated with azithromycin, 1 gm, in the field, and 9 female sex partners were treated, 7 of whom were CT positive. The cost per specimen obtained and per CT infection identified was $103 and $1,677, respectively. The annual cost for adding a peer teen outreach service to an existing STD program using existing staff and adding 1.2 full-time equivalents of outreach time is approximately $25,000. CONCLUSION: Peer teen outreach and in-field collection of urine specimens appear to be an acceptable alternative for screening teen males for CT and should be further evaluated in other communities.

Adolescent↗
PubMed1998

Domestic violence in the workplace.

1. It is important for workers, management, and health and safety personnel to recognize a history of domestic violence may place an individual at risk for acts of violence at work. 2. Employers and unions are beginning to recognize domestic violence may impact the economic well being of a workplace by decreasing productivity and attendance, and by increasing insurance and health care costs. 3. Few companies have policies related to general safety, general workplace violence, or specifically to domestic violence. All departments within the corporation or business should help to develop and implement these policies, and training in the policies must include all levels of the business.

Domestic Violence↗
PubMed1997

Cerebral cortical astroglia from the trisomy 16 mouse, a model for down syndrome, produce neuronal cholinergic deficits in cell culture.

Trisomy 21 (Down syndrome) is associated with a high incidence of Alzheimer disease and with deficits in cholinergic function in humans. We used the trisomy 16 (Ts16) mouse model for Down syndrome to identify the cellular basis for the cholinergic dysfunction. Cholinergic neurons and cerebral cortical astroglia, obtained separately from Ts16 mouse fetuses and their euploid littermates, were cultured in various combinations. Choline acetyltransferase activity and cholinergic neuron number were both depressed in cultures in which both neurons and glia were derived from Ts16 fetuses. Cholinergic function of normal neurons was significantly down-regulated by coculture with Ts16 glia. Conversely, neurons from Ts16 animals could express normal cholinergic function when grown with normal glia. These observations indicate that astroglia may contribute strongly to the abnormal cholinergic function in the mouse Ts16 model for Down syndrome. The Ts16 glia could lack a cholinergic supporting factor present in normal glia or contain a factor that down-regulates cholinergic function.

Animals↗
PubMed1997

Cholinergic stimulation increases thrombin activity and gene expression in cultured mouse muscle.

Activity-dependent synapse reduction is a major determinant of neuromuscular innervation. Previous research has shown that nanomolar concentrations of hirudin, a specific thrombin antagonist, significantly attenuates this reduction, and protease nexin 1 (PN1), an endogenous thrombin inhibitor closely localized to the neuromuscular synapse, can inhibit synapse reduction at similar concentrations. Protease inhibitors which do not inhibit thrombin, including cystatin and aprotinin, had no effect on synapse reduction. We present a series of experiments examining whether prothrombin and/or PN1 gene expression, as well as thrombin activity, are regulated in muscle cultures by acetylcholine (ACh) receptor activation. We also studied the effect of exogenous thrombin on synapse elimination in co-cultures of muscle and cholinergic neurons. Cultured muscle cells were electrically blocked with tetrodotoxin (TTX), or co-treated with ACh in order to isolate ACh receptor activation. Electrical blockade resulted in a decrease in thrombin release to about two-thirds of control values. The application of ACh to electrically blocked muscle cultures resulted in a 2.5-fold increase in thrombin activity released into the medium and a 2-fold increase in prothrombin gene expression. In contrast, ACh treatment in the presence of TTX had no effect on PN1 gene expression compared to treatment with TTX alone. In addition, exogenous thrombin significantly increased synapse elimination in unstimulated muscle/cholinergic neuron co-cultures. These results suggest that thrombin or a thrombin-like molecule released from muscle is required for activity-dependent synapse elimination and is regulated by neuromuscular activity.

Acetylcholine↗
PubMed1997

Processing of the gap junction protein connexin50 in the ocular lens is accomplished by calpain.

Gap junction channel forming connexins share a common membrane topology which has four transmembrane spanning segments with the amino- and carboxy termini both located on the cytoplasmic side. Both, mutation and truncation of the carboxyl tail of some connexins have been shown previously to have profound effects on channel function. Truncation of the carboxyl tail of connexin50 (Cx50) and connexin46 (Cx46) occurs naturally during the maturation of fiber cells in the mammalian lens. This system therefore offers the unique opportunity to study not only the cleavage process but also the functional role played by the cleaved domain, in a physiologically relevant context. As a first step, we now report on the cleavage of the 70 kDa ovine isoform of Cx50. The calcium-activated neutral protease calpain (EC 3.4.22.17) was identified as the enzyme which removed a 32 kDa carboxyl portion from the Cx50 molecule in mature lens fiber cells. The amino-terminal 38 kDa portion remained embedded in the plasma membrane and was isolated and visualized as channel structures. The amino-terminal sequence of the cleaved 32 kDa portion matched an interior portion of the published amino acid sequence of the ovine Cx50 isoform. Thus, two closely spaced calpain cleavage sites were identified in the Cx50 molecule which were located carboxy-terminal from the predicted exit of the fourth transmembrane spanning segment by 62 or 72 amino acid residues, respectively. These data provide the basic information required for the future construction of Cx50 mutants to explore the functional consequences of this cleavage.

Amino Acid Sequence↗
PubMed1994

Proteolytic activity, synapse elimination, and the Hebb synapse.

The Hebb synapse has been postulated to serve as a mechanism subserving both regulation of synaptic strength in the adult nervous system (long-term potentiation and depression) and developmental activity-dependent plasticity. According to this model, pre- and postsynaptic temporal concordance of activity results in strengthening of connections, while discordant activity results in synapse weakening. Evidence is presented that proteases and protease inhibitors may be involved in modification of synaptic strength. This leads to a modification of the Hebb assumptions, namely that postsynaptic activity results in protease elaboration with a consequent general reduction of synaptic connections to the active postsynaptic element. Further, presynaptic activity, if strong enough, induces local release of a protease inhibitor, such as protease nexin I, which neutralizes proteolytic activity and produces a relative preservation of the active input. This formulation produces many of the effects of the classical Hebbian construction, but the protease/inhibitor model suggests additional specific mechanistic features for activity-dependent plasticity.

Amyloid beta-Protein Precursor↗
PubMed1994

Triage in a vacuum.

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Emergency Nursing↗
PubMed1993

Role of tachykinins in ozone-induced acute lung injury in guinea pigs.

To examine the hypothesis that the acute reversible changes caused by ozone (O3) exposure are mediated by tachykinin release, guinea pigs were depleted of tachykinins by use of repeated capsaicin (CAP) injections before O3 exposure in an attempt to prevent O3-induced functional changes. Unexpectedly, CAP pretreatment caused divergent results in the functional responses to O3. Ventilatory measurements obtained from CAP-pretreated O3-exposed (CAP-O3) animals were exacerbated rather than diminished compared with the effects of O3 alone. Similarly, lavage fluid protein accumulation was enhanced in the CAP-O3 group compared with the O3-exposed group. In better agreement with our initial hypothesis, the CAP-O3 group was less responsive than the O3-exposed animals to histamine aerosol challenge. Additionally, Evans blue dye accumulation, a hallmark of tachykinin release, was increased in O3-exposed animals and was partially blocked in the CAP-O3 group. These data suggest that tachykinin-containing sensory fibers are unlikely to mediate the acute effects of O3 exposure on tidal breathing and lavage fluid protein accumulation but may play a role in causing post-O3 airway hyperreactivity and protein extravasation into the trachea.

Animals↗
PubMed1993

An update on the diagnosis and management of pediatric asthma. Based on the National Heart, Lung and Blood Institute expert panel report.

Asthma morbidity and mortality are increasing despite the availability of antiasthma medicines and a broader understanding of the pathology of the disease. In an attempt to enhance the understanding of asthma and to aid in appropriate asthma management, the National Heart, Lung and Blood Institute assembled an expert panel, which developed a report titled "Guidelines for the Diagnosis and Management of Asthma." These guidelines are designed to facilitate patient and health-care-provider education, and diagnosis and management of asthma. Proper diagnosis of the disease is a frequent problem in children and adults. For proper diagnosis of asthma, a complete patient history, physical examination and specific laboratory tests are required. Health care providers who educate patients and their families about common symptom triggers, encourage avoidance techniques and who incorporate state-of-the-art treatment for acute and chronic asthma management may reduce the recent increases in asthma morbidity and mortality while maintaining normal growth and development of the child.

Academies and Institutes↗
PubMed1992

Characterization of a major neutralization domain of Ross river virus using anti-viral and anti-peptide antibodies.

The E2 glycoprotein of the alphavirus Ross River virus (RRV) contains three defined neutralization epitopes (a, b1 and b2) with determinants located between amino acids 216 and 251 in the linear sequence (Vrati et al., 1988, Virology 162, 346-353). The antigenic structure of this region has been examined using hyperimmune mouse antiserum against RRV and antiserum against four synthetic peptides representing linear amino acid sequences in the neutralization region of E2. In plaque reduction neutralization tests using hyperimmune antiserum to RRV, an RRV mutant altered at all three neutralization epitopes was markedly more resistant than the parental virus; variants altered at single epitopes could not be distinguished in these tests. Sera from mice immunized with synthetic RRV E2 peptides conjugated to keyhole limpet haemocyanin reacted, in a direct ELISA, with the specific region of RRV represented by the peptide. The same sera did not neutralize or immunoprecipitate RRV in solution or bind to RRV in a capture ELISA. The RRV peptides did not prime mice to react to a subimmunogenic dose of RRV; they did not bind monoclonal or polyclonal antibodies to RRV. We conclude that a significant proportion of the neutralizing antibody response in mice is elicited by epitopes a, b1, and b2 of RRV E2 and that the sites to which neutralizing antibodies bind are formed by complex folding.

Animals↗
PubMed1992

Color Doppler ultrasonography in the evaluation of the acute scrotum.

Color Doppler ultrasonography was used to assess 20 patients with the acute onset of scrotal pain. Patients were categorized into 3 groups according to the initial clinical impression of the examining physician: ischemia, inflammation or trauma. Color Doppler ultrasonography correctly predicted the need for surgery in 8 of 9 operated patients (89%) and correctly predicted the outcome in all 11 nonoperated patients (100%). The anatomical resolution possible, as well as information regarding blood flow made color Doppler ultrasonography a useful tool in the assessment of acute scrotal processes.

Acute Disease↗
PubMed1992

Heterogeneous calcium currents and transmitter release in cultured mouse spinal cord and dorsal root ganglion neurons.

1. Calcium currents and transmitter release were studied in cocultures of fetal mouse neurons from the ventral half of the spinal cord (VH neurons) and from dorsal root ganglion (DRG neurons). The effects of BayK 8644 and omega-conotoxin on calcium currents and transmitter release were compared. 2. The presence of low voltage-activated (LVA) calcium current in both VH and DRG neurons is variable. Some cells exhibit only high voltage-activated (HVA) currents, whereas others show both HVA and LVA currents. 3. BayK 8644 did not affect LVA currents but strongly augmented both steady and transient components of the HVA calcium conductance. 4. omega-Conotoxin GVIA reduces both transient and steady components of the HVA but does not abolish either component even after 3 h of application. 5. Calcium currents that were resistant to omega-contoxin were augmented by BayK 8644. 6. Synaptic transmission between pairs of spinal cord neurons from the ventral half of the spinal cord (VH-VH connections) or between dorsal root ganglion neurons and VH neurons (DRG-VH connections) were studied with two-cell recording and stimulation techniques. 7. In approximately 70% of VH-VH connections and 50% of DRG-VH connections, BayK 8644 or its active optical isomer failed to affect transmitter output. Substantial augmentation of the remainder of the connections could be reliably produced by the dihydropyridines. Raised calcium in the extracellular medium produced augmentation of synaptic connections in all cases. BayK 8644 produced substantial, consistent augmentation of voltage-sensitive calcium channels in both VH and DRG neurons. 8. The toxin, omega-conotoxin, produced no consistent effect on excitatory or inhibitory postsynaptic potentials (EPSPs or IPSPs) elicited in VH neurons by stimulation of nearby VH neurons. VH EPSPs elicited by stimulation of nearby DRG neurons were reduced to approximately 50% of control values after 10 min of omega-conotoxin perfusion. Spontaneous and evoked synaptic activity could be recorded in VH neurons as long as 2 h after cultures were incubated in 0.5 microM omega-conotoxin. omega-Conotoxin produced a modest reduction in HVA currents in both VH and DRG neurons. 9. BayK 8644 did not produce consistent augmentation of transmission at the frog neuromuscular junction. omega-Conotoxin produced total blockade of transmission in this preparation. 10. We conclude that neither sustained nor inactivating high-threshold voltage-sensitive (HVA) calcium channels sensitive to BayK 8644 or omega-conotoxin such as those measured in the neuronal cell bodies are responsible for action-potential-evoked transmitter release from the majority of VH neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Chronic exposure to a simulated urban profile of ozone alters ventilatory responses to carbon dioxide challenge in rats.

Male Fischer 344 rats were exposed to a simulated urban profile of ozone (O3) (9-hr ramped spike, integrated concentration = 0.19 ppm) for up to 78 weeks. Small, but statistically significant, changes in breathing patterns and mechanics in unanesthetized, restrained rats were observed at Weeks 1, 3, 13, 52, and 78 during postexposure challenge with 0, 4, and 8% carbon dioxide (CO2). The data indicate that O3 exposure caused an overall increase in expiratory resistance (Rc), but particularly at 78 weeks. This increase in Rc most likely accounts for the rats' reduced ability to increase ventilation during CO2 challenge compared to control rats. Reductions in CO2-induced tidal volume increases were observed in all O3-exposed animals during postexposure challenges to 4 and 8% CO2. Cumulatively, over all time points, spontaneous frequency of breathing and CO2-induced hyperventilation were also reduced. The decrease in frequency was dependent on a significant increase in the inspiratory time relative to control without a change in expiratory time. Light microscopic evaluation of the lung did not reveal any lesions associated with O3 exposure at any time point. Although statistically significant effects were detected, the etiology of the above-mentioned functional changes remains speculative. The potential relevance of these data to acute and chronic O3 exposure in humans is also discussed.

Aging↗
PubMed1991

The effect of capsaicin on gallbladder fluid absorption.

The role of the enteric nervous system of the gallbladder on mucosal water absorption was evaluated by intraluminal administration of capsaicin, a selective stimulant of afferent nerve endings. It has been postulated that the neural responses of the gallbladder are peptidergic and mediated by prostanoids. Anesthetized cats underwent gallbladder perfusion with a physiological buffer solution containing 14C polyethylene glycol as a nonabsorbable tracer to quantitate mucosal water absorption. Capsaicin was added to the perfusate and administered intraluminally at a rate of 5 mg/kg-1/hr-1 for 2 hr. One experiment on five cats was performed when capsaicin was administered and five control experiments were performed when only vehicle was added to the perfusate. Five experiments were performed when indomethacin was administered intravenously (5 mg/kg-1/hr-1) and buffer solution alone was used to perfuse the gallbladder, and five experiments were performed when capsaicin was added to the perfusate and indomethacin was administered intravenously. Additional experiments were performed when lidocaine was added to the perfusate and when lidocaine and capsaicin were administered simultaneously. Gallbladder absorption and perfusate and tissue prostaglandin E and 6 keto prostaglandin F1 alpha concentrations were evaluated. To determine whether capsaicin induced gallbladder inflammation, tissue myeloperoxidase concentrations were measured. Control feline gallbladders absorbed approximately 0.6 ml/hr. Indomethacin alone significantly decreased gallbladder absorption. Capsaicin administration increased gallbladder absorption to approximately 1.6 ml/hr, and this increase was significantly inhibited by indomethacin. (ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗