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Biomedical subjects

J Abbott

Publications and source records attributed to J Abbott.

At least 19 recordsLinked to original sources
PubMed1996

Receptor recognition and specificity of interleukin-8 is determined by residues that cluster near a surface-accessible hydrophobic pocket.

To determine the regions of interleukin-8 (IL-8) that allow high affinity and interleukin-8 receptor type 1 (IL8R1)-specific binding of chemokines, we produced chimeric proteins containing structural domains from IL-8, which binds to both IL8R1 and interleukin-8 receptor type 2 (IL8R2) with high affinity, and from GRO gamma, which does not bind to IL8R1 and binds to IL8R2 with reduced affinity. Receptor binding activity was tested by competition of 125I-IL-8 binding to recombinant IL8R1 and IL8R2 cell lines. Substitution into IL-8 of the GRO gamma sequences corresponding to either the amino-terminal loop (amino acids 1-18) or the first beta-sheet (amino acids 18-32) reduced binding to both IL8R1 and IL8R2. The third beta-sheet of IL-8 (amino acids 46-53) was required for binding to IL8R1 but not IL8R2. Exchanges of the second beta-sheet (amino acids 32-46) or the carboxyl-terminal alpha-helix (amino acids 53-72) had no significant effect. When IL-8 sequences were substituted into GRO gamma, a single domain containing the second beta-sheet of IL-8 (amino acids 18-32) was sufficient to confer high affinity binding for both IL8R1 and IL8R2. The amino-terminal loop (amino acids 1-18) and the third beta-sheet (amino acids 46-53) of IL-8 had little effect when substituted individually but showed increased binding to both receptors when substituted in combination. Individual amino acid substitutions were made at positions where IL-8 and GRO gamma sequences differ within the regions of residues 11-21 and 46-53. IL-8 mutations L49A or L49F selectively inhibited binding to IL8R1. Mutations Y13L and F21N enhanced binding to IL8R1 with little effect on IL8R2. A combined mutation Y13L/S14Q selectively decreased binding to IL8R2. Residues Tyr13, Ser14, Phe21, and Lys49 are clustered in and around a surface-accessible hydrophobic pocket on IL-8 that is physically distant from the previously identified ELR binding sequence. A homology model of GRO gamma, constructed from the known structure of IL-8 by refinement calculations, indicated that access to the hydrophobic pocket was effectively abolished in GRO gamma. These studies suggest that the surface hydrophobic pocket and/or adjacent residues participate in IL-8 receptor recognition for both IL8R1 and IL8R2 and that the hydrophobic pocket itself may be essential for IL8R1 binding. Thus this region contains a second site for IL-8 receptor recognition that, in combination with the Glu4-Leu5-Arg6 region, can modulate receptor binding affinity and IL8R1 specificity.

Amino Acid Sequence↗
PubMed1996

Pulsed electromagnetic fields influence hyaline cartilage extracellular matrix composition without affecting molecular structure.

Pulsed electromagnetic fields (PEMF) influence the extracellular matrix metabolism of a diverse range of skeletal tissues. This study focuses upon the effect of PEMF on the composition and molecular structure of cartilage proteoglycans. Sixteen-day-old embryonic chick sterna were explanted to culture and exposed to a PEMF for 3 h/day for 48 h. PEMF treatment did not affect the DNA content of explants but stimulated elevation of glycosaminoglycan content in the explant and conserved the tissue's histological integrity. The glycosaminoglycans in sterna exposed to PEMF were indistinguishable from those in controls in their composition of chondroitin sulfate resulting from chondroitinase ABC digestion. Specific examination with [35S]-sulfate labels showed that PEMF treatment significantly suppressed both the degradation of pre-existing glycosaminoglycans biosynthetically labeled in ovo and the synthesis of new [35S]-sulfated glycosaminoglycans. The average size and aggregating ability of pre-existing and newly synthesized [35S]-sulfated proteoglycans extracted with 4 M guanidinium chloride from PEMF-treated cartilage explants were identical to controls. The chain length and degree of sulfation of [35S]-sulfated glycosaminoglycans also were identical in control and PEMF-treated cultures. PEMF treatment also reduced the amount of both unlabeled glycosaminoglycans and labeled pre-existing and newly synthesized [35S]-sulfated glycosaminoglycans recovered from the nutrient media. [35S]-Sulfated proteoglycans released to the media of both control and PEMF-treated cultures were mostly degradation products although their glycosaminoglycan chain size was unchanged. These results demonstrate that exposure of embryonic chick cartilage explants to PEMF for 3 h/day maintains a balanced proteoglycan composition by down-regulating its turnover without affecting either molecular structure or function.

Animals↗
PubMed1995

Domestic violence against women. Incidence and prevalence in an emergency department population.

OBJECTIVE: To determine the incidence, 1-year prevalence, and cumulative prevalence of domestic violence (DV) among female emergency department (ED) patients. DESIGN: Descriptive written survey. SETTING: Two teaching EDs, two hospital walk-in clinics, and one private hospital ED in Denver, Colo. PARTICIPANTS: Of 833 women presenting during 30 randomly selected 4-hour time blocks, 648 (78%) agreed to participate. Most respondents were young (median age, 34 years) and unemployed (62%); half (49%) had annual household incomes less than $10,000. MAIN OUTCOME MEASURES: Domestic violence was defined as an assault, threat, or intimidation by a male partner. Acute DV (incidence) and past DV exposure (1-year prevalence and cumulative prevalence) were determined. RESULTS: The incidence of acute DV among the 418 women with a current male partner was 11.7% (95% confidence interval [CI], 8.7% to 15.2%). Only 11 (23%) of these 47 women subjected to acute DV presented for care because of trauma, and only six (13%) either told staff about DV or were asked about DV by ED professionals. Among 230 women without current partners, 13 (5.6%) reported an episode of DV within the previous 30 days. For the entire sample, the cumulative lifetime prevalence of DV exposure was 54.2% (95% CI, 50.2% to 58.1%). Women exposed to acute or prior DV were more likely than unexposed women to have made suicide attempts (26% vs 8%; P < .001) and to report excessive ethanol use (24% vs 13%; P = .001). CONCLUSIONS: The incidence of acute DV is not as common among women visiting an ED as previously reported, although the cumulative prevalence of DV is strikingly high. Women who have experienced DV are seldom identified by ED professionals.

Adult↗
PubMed1995

Obstetric outcome after failed termination of pregnancy--a report of two cases.

Unsuccessful therapeutic abortion resulting in continued viability of the fetus is rare. No case of a live birth after unsuccessful vacuum curettage has been published. We report two cases with persistent pregnancies after failed termination, with outcomes complicated by premature rupture of membranes and preterm delivery.

Abortion, Therapeutic↗
PubMed1995

Clinical and microscopic diagnosis of vaginal yeast infection: a prospective analysis.

STUDY OBJECTIVES: To evaluate the accuracy of clinical findings and direct microscopy in the diagnosis of yeast vaginitis. DESIGN: Prospective. SETTING: Urban teaching hospital emergency department and walk-in clinic. PARTICIPANTS: Seventy-one consecutive nonmenstruating women with a presenting complaint of vaginal discharge, itching, or pain. INTERVENTIONS: Trained emergency physicians and nurse practitioners, blinded to culture results, collected clinical information, examined vaginal secretions, and obtained yeast cultures. Treatment was based on clinical impression and not altered by the study. Associations between clinical and laboratory parameters and yeast culture results were evaluated. RESULTS: Twenty-three patients (32.4%) had positive yeast cultures. Accepted risk factors were seen in patients with and without culture-positive yeast vaginitis. Clinical criteria for yeast vaginitis--including pruritus, caseous discharge, perineal edema or erythema, and patient self-diagnosis--were more common in women with yeast vaginitis but were seen with other causes of vaginitis. Watery discharge and amine odor (negative "whiff" test) were good predictors of an alternative diagnosis, but, again, accuracy was poor. Gram stain showing yeast was the most accurate laboratory method of diagnosis. Saline microscopy, potassium hydroxide, and methylene blue were all equal and only moderately accurate, with a significant proportion of false-negative and false-positive results. CONCLUSION: Standard criteria for diagnosis of monilial vaginitis are relatively unreliable. Gram stain, absence of watery discharge, and patient self-diagnosis of "another yeast infection" are the best independent predictors of a positive culture.

Adolescent↗
PubMed1995

Psychological and cardiovascular predictors of anaesthesia induction, operative and post-operative complications in minor gynaecological surgery.

This study aimed to clarify the pre-operative-personality-post-operative-recovery association by considering anaesthetic variables. Additionally, the work investigated the relationships between psychological and cardiovascular functioning and anaesthetic induction difficulties and operative problems. Two minor gynaecological procedures were evaluated (dilatation and curettage, laparoscopy) which differ greatly in anaesthetic and operative techniques. Psychological factors predicted cardiovascular responding immediately prior to the induction of anaesthesia, and combinations of cardiovascular and psychological variables were associated with anaesthetic induction, operative and post-operative problems. Health locus of control and worry concerning the various stages of the operation emerged as the most consistent psychological predictors of peri-operative outcome in both procedures.

Adolescent↗
PubMed1995

Different perceptions of disease severity and self care between patients with cystic fibrosis, their close companions, and physician.

BACKGROUND: An investigation was carried out to determine whether patients with cystic fibrosis, their close companions, and physician perceived the severity of the disease and the level of patient self care similarly. METHODS: Sixty adults with cystic fibrosis (16-44 years), their close companion, and physician independently completed scales measuring their perceptions of disease severity and patient self care on three occasions over a two year period. Percentage predicted forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), Shwachman score, and weight for height were recorded following each assessment. RESULTS: Patients and close companions considered the disease to be less severe than their physician. Fifty patients (83%) rated their health as "above/well above average", and 49 (82%) close companions rated the patient's health in the same way, but only 21 (35%) patients were considered by their physician to have mild disease. Differences also emerged in the estimation of patient self care; 48 close companions (80%) rated patients as "very good" or "excellent" in their self care, compared with 26 (44%) of the patients themselves. Only nine patients (15%) were considered to achieve this level of self care by their physician. Over the two year period the physician's ratings of severity increased in accordance with the decline in lung function. Patients' perceptions remained unchanged. CONCLUSIONS: From the physician's view-point, patients and close companions underestimate the severity of cystic fibrosis and overestimate patient self care. Patients' perceptions remain constant over time even when their health is clinically deteriorating.

Adolescent↗
PubMed1994

First trimester maternal serum pregnancy-associated plasma protein A and pregnancy-specific beta 1-glycoprotein in fetal trisomies.

OBJECTIVE: To examine the potential value of maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta 1-glycoprotein (SP1) in the detection of fetal trisomy. DESIGN: Cross-sectional study. SETTING: The Harris Birthright Research Centre For Fetal Medicine, King's College Hospital Medical School, London, UK and Division of Maternal-Fetal Medicine, Jefferson Medical College, Philadelphia, USA. SUBJECTS AND METHODS: Maternal serum PAPP-A and SP1 concentrations were measured at 10 to 13 weeks gestation in samples from 42 pregnancies with fetal trisomy (trisomy 21, n = 29; trisomy 18, n = 9; trisomy 13, n = 4) and in samples from 210 matched controls. RESULTS: In controls, both maternal serum PAPP-A and SP1 increased significantly with gestation and in trisomic fetuses levels of both hormones were reduced. However, discriminant analysis demonstrated that SP1 did not contribute significantly in the distinction between trisomic and control pregnancies. Although levels of PAPP-A were reduced throughout the gestational range examined (10 to 13 weeks), especially in cases with fetal trisomy 21, the deviation was more pronounced at 10 to 11 weeks than at 12 to 13 weeks gestation. In 45% of pregnancies with fetal trisomy 21 and 70% of pregnancies with trisomies 18 or 13 maternal serum PAPP-A levels at 10 to 11 weeks gestation were below the 5th centile of the normal range. CONCLUSION: Maternal serum PAPP-A concentration in the first trimester of pregnancy may prove to be useful in the prediction of risk for fetal trisomies.

Adult↗
PubMed1994

Treatment compliance in adults with cystic fibrosis.

BACKGROUND: The study comprised three interrelated aims: (1) to ascertain (a) patient compliance with physiotherapy, exercise, enzyme and vitamin regimens, (b) how compliance was perceived by patients, and (c) the reasons for poor compliance (2) to identify demographic and clinical variables associated with compliance; and (3) to determine how accurately patient compliance can be predicted by carers. METHODS: Demographic and medical history data were obtained from medical records and a patient questionnaire. The data obtained included age, sex, employment status, inpatient or outpatient status, frequency of contact with the clinic, age at diagnosis, and the number of years practising physiotherapy. Measures of clinical status, including FEV1 and FVC percentage predicted, Shwachman score, and 24 hour sputum weight were recorded before completion of the questionnaire. The questionnaire, administered by a psychologist, assessed the reported degree of patient compliance, their perception of compliance, and their reasons for poor compliance. RESULTS: Sixty patients participated in the study and 51/60 and 41/55 patients were considered compliant with enzyme and exercise therapies, respectively. Compliance was lower with physiotherapy (32/60) and vitamin treatment (21/45). Patients reporting immediate benefits following exercise and physiotherapy were more compliant than those reporting no improvement. The perception by patients that compliance was sufficient ("about right") was physiotherapy 67%, exercise 37%, enzymes 78%, and vitamins 9%. Compliance was not influenced by demographic details nor by severity of disease, although patients producing large amounts of sputum and receiving help with physiotherapy were more compliant with physiotherapy. The physiotherapist and physician judged correctly the degree of compliance with physiotherapy in 83% and 75% of cases, respectively, and with exercise in 68% and 67% of cases, respectively. CONCLUSIONS: The reported degree of compliance and reasons for poor compliance were treatment specific. Demographic and disease severity variables were not associated with compliance. Those involved in the care of patients with cystic fibrosis were able to predict patient compliance.

Adolescent↗
PubMed1994

Medical illness during pregnancy.

Several medical illnesses commonly occur in the pregnant patient admitted to the emergency department. Some, such as hyperemesis gravidarum and urinary tract infection, occur exclusively or with increased frequency in pregnancy. Thromboembolic disease is the leading cause of maternal death in pregnancies that survive the first 3 months. Sickle cell disease, seizures, diabetes, and asthma are common in young women, and the emergency physician needs to know the ways in which pregnancy alters presentation and management of these illnesses.

Chronic Disease↗
PubMed1993

Cooperative binding of the Escherichia coli repressor of biotin biosynthesis to the biotin operator sequence.

Regulation of biotin biosynthesis and retention in Escherichia coli depends on a complex set of coupled protein-protein, protein-nucleic acid, and protein-small molecule interactions. The complexity of the biotin system is analogous to that found in gene regulatory systems from other prokaryotes and from eukaryotes. Quantitative understanding of these systems requires thermodynamic studies of the individual contributing interactions. We have initiated such studies of the biotin regulatory interactions. The assembly states of the biotin operon repressor (BirA) and its complex with the allosteric effector, bio-5'-AMP, have been determined by analytical gel filtration chromatography. Both the apo- and holo-repressors are monomeric at protein concentrations several orders of magnitude higher than those required for DNA binding. Results of stoichiometric DNA binding measurements indicate that the BirA-biotin operator (bioO) complex consists of two holo-repressor monomers per operator site. Equilibrium binding of BirA to bioO has been measured using the quantitative DNase footprint technique. Analysis of the data indicates that the binding process is best described by a cooperative model. An upper limit for the cooperative free energy is estimated to be between -2.0 and -3.0 kcal/mol.

Adenine Nucleotides↗
PubMed1993

Ruptured ectopic pregnancy after medical management: current conservative management strategies.

A case of hypotension caused by hemorrhage in a patient receiving systemic methotrexate to treat a known ectopic pregnancy is presented. A primary goal of gynecologic practice in the 1990s is to conserve tubal patency and fertility. Consequently, ectopic pregnancy is more frequently being managed by conservative strategies. The emergency physician must be familiar with conservative methods for the management of ectopic pregnancy and the complications that may cause emergency presentations in these patients.

Adult↗
PubMed1993

Loss and grief reactions after spontaneous miscarriage in the emergency department.

STUDY OBJECTIVE: To describe the psychological and functional consequences of miscarriage in women after emergency department treatment and to identify variables that are associated with feelings of loss and grief. DESIGN: A prospective telephone follow-up study. SETTING: The ED of an urban teaching hospital. TYPE OF PARTICIPANTS: A consecutive sample of 44 women who were treated for miscarriage. MAIN RESULTS: Women were contacted a median of 17.5 days after their miscarriage. Although the pregnancy had been planned by only 12 women (28%), 30 (70%) stated they wanted the pregnancy once they knew they were pregnant. Women commonly felt a sense of loss (82%) and most experienced some limitations with daily functioning (77%). Although wanting the pregnancy was associated with a sense of loss, 40% of the women who did not want the pregnancy experienced loss. CONCLUSION: Grief reactions are pervasive after spontaneous miscarriage. There is no subgroup of women who could be expected not to experience loss and grief. The ED management of the woman who miscarries should address the anticipated loss and grief.

Abortion, Spontaneous↗
PubMed1993

Early experience with dobutamine stress testing and cardiac cine-tomographic imaging in the elderly: antianginal effects of nifedipine-GITS.

OBJECTIVE: To determine the effects of nifedipine-GITS (GITS = gastrointestinal transport system) on angina and cardiovascular responses to stress-dobutamine infusion, we used ultrafast cine-computed tomography (CT) to assess regional wall motion, myocardial perfusion, and indices of ventricular filling and emptying. DESIGN: Randomized, double-blind placebo-controlled efficacy study after an open-label dose titration phase. SETTING: University of California, San Francisco. PATIENTS: Elderly patients (> 60 years; n = 9:8 male, 1 female) with coronary artery disease by history and diagnostic treadmill or coronary angiography. INTERVENTION: After a 3-week open-label dose-titration phase, eight subjects were randomized to receive either placebo or nifedipine-GITS at the highest tolerated dose for 2 weeks, followed by a crossover to the alternate therapy for 2 weeks. One declined because of singulus in the open-label period. MAIN OUTCOME MEASURES: Symptomatic angina relief (frequency and nitroglycerin consumption), dobutamine stress responses (time to ischemia during dobutamine infusions, cardiac output, cardiac ejection fraction, ventricular segmental wall motion, and perfusion as measured by ultrafast cine-CT), and reported adverse effects. RESULTS: When compared with placebo, nifedipine-GITS administration was associated with less frequent angina and nitroglycerin consumption (NS) and significantly decreased systolic blood pressure. Nifedipine-GITS administration also increased resting supine heart rates. Dobutamine infusions increased heart rate, cardiac output, cardiac ejection fraction, and stroke volume and induced angina symptoms. Neither double product at angina nor systolic indices of cardiac function in response to dobutamine differed between nifedipine-GITS and placebo, although heart rate responses were greater during nifedipine. A trend toward increased peak filling rates was seen during dobutamine stress in the nifedipine-administration period. In most subjects (6/8), perfusion and regional wall motion abnormalities were not visualized on regional wall motion abnormalities were not visualized on either rest or stress cine-CT studies. Edema without congestive heart failure occurred frequently during nifedipine-GITS administration. CONCLUSIONS: These data suggest that (1) dobutamine stress can be used to induce cardiac ischemia in elderly patients with coronary artery disease, (2) nifedipine-GITS provides symptomatic angina relief in elderly patients, (3) peripheral edema is frequent in elderly patients on nifedipine-GITS, and (4) ultrafast computed cine-tomography testing can be used to assess ventricular performance, but current methodology may not detect perfusion or wall motion abnormalities during angina.

Age Factors↗
PubMed1993

Making the commitment to managed care.

To develop and to implement managed care requires support from key participants including administrators, physicians, nurse managers and all healthcare providers. This multidisciplinary approach assures success and increases support when making the move toward managed care.

Goals↗