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Biomedical subjects

E Miller

Publications and source records attributed to E Miller.

At least 127 records · Page 7Linked to original sources

Parenteral nutrition in the management of a dog with lymphocytic-plasmacytic enteritis and severe protein-losing enteropathy.

Management of lymphocytic-plasmacytic enteritis in a dog with whipworm infestation, hypoproteinemia, and ascites is described. Short-term parenteral nutrition hastened normalization of serum proteins, resolution of diarrhea, and weight gain. A description of the potential benefits, limitations, and possible complications of parenteral nutrition in refractory inflammatory bowel disease is given.

Animals↗

Endoplasmic reticulum stress proteins block oxidant-induced Ca2+ increases and cell death.

Oxidants are important human toxicants. Increased intracellular free Ca2+ may be critical for oxidant toxicity, but this mechanism remains controversial. Furthermore, oxidants damage the endoplasmic reticulum (ER) and release ER Ca2+, but the role of the ER in oxidant toxicity and Ca2+ regulation during toxicity is also unclear. tert-Butylhydroperoxide (TBHP), a prototypical organic oxidant, causes oxidative stress and an increase in intracellular free Ca2+. Therefore, we addressed the mechanism of oxidant-induced cell death and investigated the role of ER stress proteins in Ca2+ regulation and cytoprotection after treating renal epithelial cells with TBHP. Prior ER stress induces expression of the ER stress proteins Grp78, Grp94, and calreticulin and rendered cells resistant to cell death caused by a subsequent TBHP challenge. Expressing antisense RNA targeted to grp78 prevents grp78 induction sensitized cells to TBHP and disrupted their ability to develop cellular tolerance. In addition, overexpressing calreticulin, another ER chaperone and Ca2+-binding protein, also protected cells against TBHP. Interestingly, neither prior ER stress nor calreticulin expression prevented lipid peroxidation, but both blocked the rise in intracellular free Ca2+ after TBHP treatment. Loading cells with EGTA, even after peroxidation had already occurred, also prevented TBHP-induced cell death, indicating that buffering intracellular Ca2+ prevents cell killing. Thus, Ca2+ plays an important role in TBHP-induced cell death in these cells, and the ER is an important regulator of cellular Ca2+ homeostasis during oxidative stress. Given the importance of oxidants in human disease, it would appear that the role of ER stress proteins in protection from oxidant damage warrants further consideration.

Animals↗

Impact of anti-vaccine movements on pertussis control: the untold story.

To assess the impact of anti-vaccine movements that targeted pertussis whole-cell vaccines, we compared pertussis incidence in countries where high coverage with diphtheria-tetanus-pertussis vaccines (DTP) was maintained (Hungary, the former East Germany, Poland, and the USA) with countries where immunisation was disrupted by anti-vaccine movements (Sweden, Japan, UK, The Russian Federation, Ireland, Italy, the former West Germany, and Australia). Pertussis incidence was 10 to 100 times lower in countries where high vaccine coverage was maintained than in countries where immunisation programs were compromised by anti-vaccine movements. Comparisons of neighbouring countries with high and low vaccine coverage further underscore the efficacy of these vaccines. Given the safety and cost-effectiveness of whole-cell pertussis vaccines, our study shows that, far from being obsolete, these vaccines continue to have an important role in global immunisation.

Global Health↗

Purification and characterization of the tetrachloroethene reductive dehalogenase of strain PCE-S.

The membrane-associated tetrachloroethene reductive dehalogenase from the tetrachloroethene-reducing anaerobe, strain PCE-S, was purified 165-fold to apparent homogeneity in the presence of the detergent Triton X-100. The purified dehalogenase catalyzed the reductive dechlorination of tetrachloroethene to trichloroethene and of trichloroethene to cis-1,2-dichloroethene with reduced methyl viologen as the electron donor, showing a specific activity of 650 nkat/mg protein. The apparent Km values of the enzyme for tetrachloroethene, trichloroethene, and methyl viologen were 10 microM, 4 microM, and 0.3 mM, respectively. SDS-PAGE revealed a single protein band with an apparent molecular mass of 65 kDa. The apparent molecular mass of the native enzyme was 200 kDa as determined by gel filtration. Tetrachloroethene dehalogenase contained 0.7 +/- 0.3 mol corrinoid, 1.0 +/- 0.3 mol cobalt, 7.8 +/- 0.5 mol iron, and 10.3 +/- 2.0 mol acid-labile sulfur per mol subunit. The pH optimum was approximately 7.2, and the temperature optimum was approximately 50 degrees C. The dehalogenase was oxygen-sensitive with a half-life of approximately 50 min. The N-terminal amino acid sequence of the enzyme was determined, and no significant similarity was found to any part of the amino acid sequence of the tetrachloroethene (PCE) reductive dehalogenase from Dehalospirillum multivorans.

Bacteria, Anaerobic↗

Hospital admissions in children due to pneumococcal pneumonia in England.

Hospital records of 116 children under 5 years of age discharged from 11 hospitals in three regions in England with a diagnosis of lobar (pneumococcal) pneumonia were reviewed to estimate the proportion likely to be attributable to infection with Streptococcus pneumoniae. Of these, 100 (86%) had lobar/focal changes on chest X-ray consistent with pneumococcal infection, although only one (1%) had pneumococcus isolated from blood. However, a further 89 (89%) with a lobar/focal picture were considered to be likely or possibly due to pneumococcal infection on the basis of the white cell count, level of C-reactive protein, isolation of the S. pneumoniae from either sputum or nasopharingeal aspirate and failure to identify another responsible pathogen. Of 135 cases with a discharge diagnosis of bronchopneumonia or pneumonia (organism unspecified), two (1%) had S. pneumoniae isolated from blood and a further 95 (70%) had clinical or laboratory features consistent with pneumococcal infection or S. pneumoniae isolated from either sputum or nasopharyngeal aspirate. With the imminent availability of conjugate pneumococcal vaccines, there is a need for improved diagnostic methods for identifying the pathogens responsible for community-acquired pneumonia in young children.

Age Distribution↗

Review of the evidence for the use of erythromycin in the management of persons exposed to pertussis.

We assessed the quality of evidence for the use of erythromycin in preventing secondary transmission of pertussis to close contacts of primary cases. A literature search was undertaken and identified papers were reviewed critically. Thirteen original papers and 1 manuscript met the inclusion criteria for review (3 randomized controlled trials, 4 analytical studies and 7 descriptive studies). Evidence from both experimental and analytical studies showed little effect of the use of erythromycin in preventing secondary transmission. Its effect is at best modest when compared with the protection conferred by use of good quality whole cell vaccine. Three studies reported adverse events with erythromycin prophylaxis; these were mainly nausea, vomiting and abdominal pain. In countries where effective pertussis vaccines are in use, erythromycin use should be confined to close contacts of cases, particularly unimmunized children or partially immunized infants who would be most susceptible to the complications of pertussis, or adults who come into close contact with vulnerable children.

Adult↗

Salivary diagnosis of rubella: a study of notified cases in the United Kingdom, 1991-4.

Rubella infections, notified by general practitioners on the basis of a clinical diagnosis, were investigated by testing blood and saliva samples for specific IgM. Overall 52 (29%) of 178 cases with appropriately timed blood specimens were confirmed as recent rubella by IgM serology. Only 2 (3%) of 74 cases in children under 5 years were confirmed compared to 50 (48%) of 104 cases in older children and adults. The confirmation rate was lower (6%) in those with documented vaccination history than in those without (42%). The specificity of saliva rubella IgM testing compared to testing corresponding blood samples was 99%. The overall sensitivity of saliva rubella IgM testing was 81%. This rose to 90% if results from inappropriately timed specimens and specimens taking more than 1 week to reach the laboratory were excluded. A corresponding saliva rubella IgG test was 98% sensitive and 100% specific. Of 126 rubella IgM negative cases, 25 (20%) were positive for parvovirus B19 IgM. This study confirmed that rubella surveillance based on clinical reports is not specific. It also demonstrated that saliva samples, if taken 7-42 days after onset of illness and transported rapidly to the laboratory, are a feasible alternative to blood samples for rubella surveillance.

Adolescent↗

Distinct T-cell subtypes induced with whole cell and acellular pertussis vaccines in children.

Recent clinical trials have demonstrated that new generation acellular pertussis vaccines can confer protection against whooping cough. However, the mechanism of protective immunity against Bordetella pertussis infection induced by vaccination remains to be defined. We have examined cellular immune responses in children immunized with a range of acellular and whole cell pertussis vaccines. Immunization of children with a potent whole-cell vaccine induced B. pertussis-specific T cells that secreted interferon-gamma (IFN-gamma), but not interleukin-5 (IL-5). In contrast, T cells from children immunized with acellular pertussis vaccines secreted IFN-gamma and/or IL-5 following stimulation with B. pertussis antigens in vitro. These observations suggest that protective immunity conferred by whole-cell vaccines, like natural immunity, is mediated by type 1 T cells, whereas the mechanism of immune protection generated with acellular vaccines may be more heterogeneous, involving T cells that secreted type 1 and type 2 cytokines.

Antigens, Bacterial↗

Antibody avidity as a surrogate marker of successful priming by Haemophilus influenzae type b conjugate vaccines following infant immunization.

Evaluation of the new generation of conjugate vaccines is hampered by the absence of reliable surrogate markers of immunologic memory. Memory responses are characterized by rapid production of relatively high-avidity antibody; thus, a solid-phase ELISA was adapted for the measurement of anti-Haemophilus influenzae type b (Hib) IgG avidity. In a cohort of infants vaccinated at 2, 3, and 4 months of age with Hib conjugate vaccines, avidity increased in the period following vaccination, while antibody titer fell. After a booster dose at 1 year of age, both antibody titer and avidity increased. In a cohort with anti-Hib IgG <1.0 microg/mL following primary immunization, antibody avidity after booster was low, indicating an absence of priming. Antibody avidity may help distinguish, in persons with low antibody titers, between those who are primed for memory and those who are not.

Antibodies, Bacterial↗

16-Epiestriol, a novel anti-inflammatory nonglycogenic steroid, does not inhibit IFN-gamma production by murine splenocytes.

All the steroidal anti-inflammatory drugs currently available are glucocorticoids. The desired anti-inflammatory activities of glucocorticoids frequently are accompanied by adverse side effects, notably glycogenic activities and profound immunosuppression, that can limit clinical use. We recently identified 16-epiestriol, a naturally occurring steroid, as exhibiting significant anti-inflammatory activity without glycogenic activity. In the present study, we compared the effects of 16-epiestriol and hydrocortisone on the capacity of murine splenocytes to produce interferon-y (IFN-y). We injected young adult male BDF1 mice once with 20 mg/kg hydrocortisone or 20, 5, or 1 mg/kg 16-epiestriol and 4 h later harvested the splenocytes. Flow cytometric analysis confirmed that 16-epiestriol did not alter the number of CD3+ T cells in the spleen. In contrast to the suppressive effects of hydrocortisone, none of the 16-epiestriol concentrations inhibited concanavalin A-stimulated IFN-gamma production by spleen cells, as determined by ELISA. Incubating spleen cells from untreated mice in concentrations of 16-epiestriol ranging from 1 mg/ml to 100 pg/ml did not alter profiles of IFN-gamma production, in contrast to the suppressive dose-response effects of hydrocortisone. Collectively, these results support the contention that 16-epiestriol may be a clinically useful safe anti-inflammatory steroid without profound immunosuppressive activities.

Adjuvants, Immunologic↗

Expression and properties of wild-type and mutant forms of the Drosophila sex comb on midleg (SCM) repressor protein.

The Sex comb on midleg (Scm) gene encodes a transcriptional repressor of the Polycomb group (PcG). Here we show that SCM protein is nuclear and that its expression is widespread during fly development. SCM protein contains a C-terminal domain, termed the SPM domain, which mediates protein-protein interactions. The biochemical function of another domain consisting of two 100-amino-acid-long repeats, termed "mbt" repeats, is unknown. We have determined the molecular lesions of nine Scm mutant alleles, which identify functional requirements for specific domains. The Scm alleles were tested for genetic interactions with mutations in other PcG genes. Intriguingly, three hypomorphic Scm mutations, which map within an mbt repeat, interact with PcG mutations more strongly than do Scm null alleles. The strongest interactions produce partial synthetic lethality that affects doubly heterozygous females more severely than males. We show that mbt repeat alleles produce stable SCM proteins that associate with normal sites in polytene chromosomes. We also analyzed progeny from Scm mutant germline clones to compare the effects of an mbt repeat mutation during embryonic vs. pupal development. We suggest that the mbt repeat alleles produce altered SCM proteins that incorporate into and impair function of PcG protein complexes.

Alleles↗

Assessing, developing, and maintaining staff's competency in times of restructuring.

Downsizing and reorganization in hospitals have resulted in nursing staff being realigned to different areas. During these times, nurse educators are continually challenged to provide effective educational programs to develop and upgrade staff competency. Nurse educators at a government health care facility in New York City experienced similar challenges as inpatient units were closed and staff had to develop or upgrade their skills. Two educational programs were designed to prepare staff to assume other duties, and competency assessments were developed and used to measure the effectiveness of the programs. Concepts relevant to competency assessment, development, and maintenance are discussed, and methods of assessments are described. Sample assessment tools and description of outcomes are included.

Clinical Competence↗