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Biomedical subjects

E Pollock

Publications and source records attributed to E Pollock.

17 recordsLinked to original sources
PubMed1999

Folding intermediates of SNARE complex assembly.

SNARE (soluble NSF attachment protein receptor) proteins assemble into a stable complex essential for vesicle-membrane fusion. To further understand SNARE function we have used solution nuclear magnetic resonance (NMR) spectroscopy to characterize three assembly states of a yeast SNARE complex: first, the 'closed' conformation of Sso1; second, the binary complex of Sso1 and Sec9; and third, the ternary complex of Sso1, Sec9 and Snc1. Sec9 and Snc1 are unstructured in isolation. Sso1 likely consists of a four helix bundle formed by part of the C-terminal Hcore domain and the N-terminal H(A)H(B)H(C) domain, and this bundle is flanked on both sides by large flexible regions. Sso1 switches to an 'open' state when its Hcore domain binds Sec9. Conformational switching of the Hcore domain, via H(A)H(B)H(C), may provide a key regulatory mechanism in SNARE assembly. Formation of binary and ternary complexes induces additional alpha-helical structure in previously unstructured regions. Our data suggest a directed assembly process beginning distal to the membrane surfaces and proceeding toward them, bringing membranes into close proximity and possibly leading to membrane fusion.

Circular Dichroism↗
PubMed1991

Use of the Pediatric Risk of Mortality score to predict nosocomial infection in a pediatric intensive care unit.

OBJECTIVE: To define infection rates in patients with Pediatric Risk of Mortality (PRISM) scores greater than and less than 10 on admission to the pediatric ICU (PICU). DESIGN: Descriptive. SETTING: An 18-bed PICU admitting patients of all ages except nonsurgical neonates; within a 585-bed tertiary care pediatric hospital. PATIENTS: Patients admitted to the PICU from July 1987 to February 1988 inclusive. Of 685 admitted, 480 were followed for greater than or equal to 72 hr. METHODS: The baseline state of the patients on admission was determined by a designated intensivist using the PRISM score. Other variables included age, length of stay, and hospital day of onset of infection. Infections were identified by a designated intensivist who undertook prospective daily bedside observation, chart, radiographic, and laboratory review. MEASUREMENTS AND MAIN RESULTS: Equal portions of patients had PRISM scores less than and greater than 10. Significantly more infections occurred in the high PRISM population (10.8% vs. 3.4%, p less than .001). This association held through age, service, and length of stay. Sensitivity, specificity, positive and negative predictive values of a PRISM score greater than 10 were 75%, 53%, 11%, and 97%, respectively. Bacteremias accounted for 36% of infections, skin/eye/drain site 22%, respiratory 16%, wound 15%, and urine 9%. The most prevalent organisms were coagulase-negative staphylococci (32%), Pseudomonas aeruginosa (23%), Candida sp. (20%), and S. aureus (9%). CONCLUSIONS: A PRISM score greater than 10 on PICU admission characterizes a population within the PICU at increased risk of infection. However, 93% of patients did not develop infection and thus, a negative predictive value of 97% yields little additional information.

Adolescent↗
PubMed1990

Then and now: how far have we come? Part I.

The political, technological and economic forces of the turbulent '80s mandated changes in the way the American healthcare sector conducted the business of caring for people. In this first of a two-part series, Computers in Healthcare examines the evolution of healthcare computing in several key application areas. Part I will explore progress in laboratory, radiology, patient accounting, case mix and patient care systems.

Hospital Information Systems↗
PubMed1990

Applications: how far have we come? Part II.

In this second of a two-part look at the evolution of critical issues and application areas, Computers in Healthcare Associate Editor Ellen Pollock examines how far integration, nursing systems, executive decision support and expert systems have come during the 1980s. Her top industry sources discuss the outlook for these applications in the near-term future, as well.

Computer Communication Networks↗
PubMed1989

Evaluation of a new method of detection of nosocomial infection in the pediatric intensive care unit: the Infection Control Sentinel Sheet System.

To improve the efficiency of nosocomial infection detection, a highly structured system combining initial reporting by the bedside night nurse of symptoms possibly related to infection with follow-up by the infection control nurse (ICN) was developed: The Infection Control Sentinel Sheet System (ICSSS). Between July 1, 1987 and February 28, 1988, a prospective comparison of results obtained through ICSSS and daily bedside observation/chart review by a full-time trained intensivist was undertaken in the pediatric intensive care unit (PICU). Ratios of nosocomial infections and nosocomially-infected patients were 15.8 and 7.0 respectively among 685 admissions; included are seven infections identified only through the ICSSS so that the "gold standard" became an amalgamation of the two systems. The sensitivity for detection of nosocomially-infected patients by bedside observation/chart review and ICSSS was 100% and 87% respectively. The sensitivity for detection of standard infections (blood, wound and urine) was 88% and 85% respectively. The sensitivity for detection of nosocomial infections at all sites was 94% and 72% respectively. Missed infections were minor (e.g., drain, skin, eye), required physician diagnosis (e.g., pneumonia), were not requested on the sentinel sheet (SS) (e.g., otitis media), related to follow-up of deceased patients or were minor misclassifications or failures to associate with device (e.g., central-line related). Daily PICU surveillance by the ICN required only 20 minutes a day. The ICSSS appears highly promising and has many unmeasured benefits.

Bias↗
PubMed1989

Automation within small hospitals: no hospital can afford to be without it.

Excessively tight operating margins, lower reimbursement policies and a higher-than-average Medicare base have put a tight economic squeeze on small hospitals. Comprehensive hospital information systems can help small hospitals get ahead of the game, yet this segment of the marketplace has been frustratingly slow to automate.

Computers↗
PubMed1989

Expert systems: fact or fantasy?

Within the last decade, much ado has been made about expert systems, a revolutionary technology that may strongly impact the delivery of healthcare. In the midst of endless discussions of the potential of expert systems, confusion nevertheless reigns supreme when it comes to understanding just exactly what this technology does and its function within the healthcare environment.

Expert Systems↗
PubMed1987

Cytogenetic and biological characterization of two new human plasma cell lines.

Two new human plasma cell lines designated as ACB-885 and ACB-1085 have been established from a 39-year-old patient with multiple myeloma. These cell lines have definitive plasma cell features by morphologic examination, and essentially all of the cells are positive for cytoplasmic IgG kappa immunoglobulin. These cells are negative for standard T-cell surface markers and mature B-cell markers, such as B1, B2, and HLA-DR, but are strongly positive for the antigen defined by OKT-10. The cells are negative for Epstein-Barr virus. The cell lines have a doubling time of 30-35 hours and a growth fraction approaching 100%. Cytogenetic analysis showed a 2n chromosome number of 45-46 with very similar karyotypic abnormalities in both the plasma cell lines and the original tumor material. One of the chromosomes in each of the pairs of chromosomes number #1, #2, #6, #7, #8, #10, #12, #13, and #22 were consistently missing. These were replaced by eight marker chromosomes that resulted from chromosomal rearrangements involving mainly these missing chromosomes. Almost all of the breakpoints occurring in the marker chromosomes were identified, and eight of these breakpoints have been reported in other studies of myeloma plasma cells. Homogeneously staining regions were observed in two marker chromosomes suggesting gene amplification in these chromosomal regions.

Cell Line↗
PubMed1987

Are the current criteria for response useful in the management of multiple myeloma?

One hundred seventy-three patients with multiple myeloma were treated from the time of diagnosis with standard oral melphalan and prednisone at 28-day intervals until they became refractory to treatment. Response to treatment was determined according to the Chronic Leukemia-Myeloma Task Force (TF) criteria, and independently according to the Southwest Oncology Group (SWOG) criteria. Survival by disease stage and response according to the two sets of criteria were analyzed for patients living longer than 3 months. The median survival of responding and nonresponding (TF criteria) stage II patients was 43.8 and 40.3 months, respectively (P = .29). By SWOG criteria, median survival for responding and nonresponding stage II patients was 48.3 and 39.0 months, respectively (P = .12). In stage III patients, median survival for responders and nonresponders (TF criteria) was 34.0 and 21.7 months, respectively (P = .01), compared with 35.5 and 24.4 months (P = .04) by SWOG criteria. These data would suggest that the TF criteria predicts a survival disadvantage only in very advanced myeloma and that applying the stricter limits for the definition of response of the SWOG does not further aid in selecting a subgroup of myeloma patients with poorer survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Loss of viability and induction of DNA damage in human leukemic myeloblasts and lymphocytes by m-AMSA.

The effects of m-AMSA on in vitro viability and on the induction of DNA damage were examined in low-growth-fraction cell populations of human leukemic myeloblasts and normal lymphocytes. A significant individual variation in the drug-induced reduction of in vitro viability was observed in studies with five selected leukemic patients. The concentration of m-AMSA required to reduce viability by 50% within 48 h ranged from 0.25 microM to in excess of 5.0 microM for the leukemic myeloblasts as against about 2.0 microM for the samples of normal lymphocytes. Alkaline elution studies showed that m-AMSA induced protein-associated DNA strand breaks (PADB) in both myeloblasts and lymphocytes. Depending upon the m-AMSA concentration, there was a 4- to 9-fold difference in the level of PADBs induced by a given drug concentration in the myeloblasts of eight patients studied. The level of PADBs was saturable with respect to both drug concentration (5-10 microM) and exposure time (45-10 microM). The PADBs were repaired rapidly in all the lymphocyte and myeloblast samples studied, with over 90% of this DNA damage being repaired within 45 min after resuspension of the cells in drug-free medium. These studies of m-AMSA in low-growth-fraction samples of human lymphocytes and myeloblasts show both similarities and differences in the action of this drug compared with previously published studies using the high-growth-fraction mouse L1210 system.

Aminoacridines↗
PubMed1985

Single-strand breaks or alkali-sensitive sites in the DNA of human myeloma plasma cells and chronic lymphocytic leukemia lymphocytes.

Alkaline-elution studies showed significant levels of either DNA single-strand breaks or alkali-sensitive sites in the plasma cells of six out of six myeloma patients and in the lymphocytes of two out of four patients with chronic lymphocytic leukemia as compared with normal human lymphocytes. The increased rate of DNA elution was variable from sample to sample with a range that would correspond to that observed with 100-1000 rad (1 rad = 10 mGy) of X-ray irradiation. This alteration in DNA structure was observed in both new and advanced patients, did not appear to be related to prior therapy, and did not affect the in vitro viability of these cells. Repetitive alkaline-elution profiles obtained with tumor cells from three patients were similar on subsequent samples obtained 1 month apart. Altered DNA elution was not evident in peripheral blood lymphocytes from myeloma patients with altered plasma cell DNA elution. These observations are interesting in light of the recent hypothesis that breaking and rejoining of DNA, regulated by poly(ADP-ribosyl)ation, may be a general mechanism of altering gene expression during differentiation.

Alkalies↗
PubMed1984

DNA strand breaks induced in human T-lymphocytes by the combination of deoxyadenosine and deoxycoformycin.

There is a progressive loss of human T-lymphocyte viability upon incubation with deoxycoformycin, an adenosine deaminase inhibitor, and low concentrations of deoxyadenosine (drug concentration that reduced cell count at 48 hr after initiation to 50% of value for untreated control culture, less than 1 microM). The loss of viability was evidenced by vital staining with fluorescein diacetate and by changes in forward single light scatter measured by flow cytometry. This loss of lymphocyte viability is detectable 18 to 20 hr after the addition of deoxyadenosine and is earlier than has been reported by other investigators using trypan blue as the vital stain. Alkaline elution studies show that the incubation of T-lymphocytes with the combinations of deoxycoformycin and deoxyadenosine gives rise to DNA single-strand breaks. These DNA strand breaks are dose and time dependent and are readily detected 4 hr after the addition of deoxyadenosine. These DNA lesions are not observed with deoxycoformycin or deoxyadenosine alone. Incubations of T-lymphocytes with deoxycoformycin and deoxyadenosine (1 and 5 microM) for 7 hr result in DNA strand breaks with a frequency of 145 and 280 rad equivalents, respectively. Preliminary studies indicate that the ability of lymphocytes to repair this damage is dependent upon deoxyadenosine concentration and exposure time. The relationship of these DNA lesions to loss of lymphocyte viability in the presence of deoxycoformycin and deoxyadenosine remains to be established.

Antineoplastic Agents↗
PubMed1982

Adenosine and deoxyadenosine toxicity in colony assay systems for human T-lymphocytes, B-lymphocytes, and granulocytes.

Adenosine and deoxyadenosine toxicity was examined in colony assay systems for human T lymphocytes, B lymphocytes, and granulocytes. In the absence of deoxycoformycin, an adenosine deaminase inhibitor, no growth inhibition was observed in the three systems with concentrations of adenosine or deoxyadenosine of at least 200 microM. Deoxycoformycin itself had no growth-inhibitory effect at concentrations of at least 10 micrograms/ml. Combinations of deoxycoformycin (1 microgram/ml) and either adenosine or deoxyadenosine gave growth inhibition in all three systems. Deoxyadenosine was the most toxic in all the systems, the LD50 values being 20-25 microM. The LD50 values for adenosine were 45-55 microM. There was no evidence of selective toxicity by adenosine or deoxyadenosine with these three colony assay systems. In the T-lymphocyte colony system deoxyadenosine appeared to be toxic to both the inducer/helper and the suppressor/cytotoxic T-lymphocyte subpopulations.

Adenosine↗