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P Simmons

Publications and source records attributed to P Simmons.

At least 19 recordsLinked to original sources

Evaluation of a school climate instrument for assessing affective objectives in health professional education.

A conceptual framework for the study of school climate and development of professional caring ability is proposed that is compatible with research on learning environment and socialization. Student input characteristics were measured demographically and through use of previously validated scales from the Parental Bonding Instrument; student outcome characteristics were measured on the Caring Ability Inventory for which considerable empirical validity evidence exists. The primary focus of this evaluation addressed reliability and validity of an instrument designed to assess learning environment that had not previously been used in postsecondary education. Four abbreviated School Climate scales were studied: Respect, Trust, Morale, and Caring. Source data were obtained from the initial phase of a longitudinal study of baccalaureate nursing students throughout the United States. Factor analysis, score reliability, and item-total correlation results indicate the School Climate instrument has indicate the School Climate instrument has theoretical and practical utility for program evaluation and improvement in health professional education.

Adult

ERISA preemption and its impact on behavioral health services.

Recently, mental health parity provisions were passed and incorporated retroactively into the Health Insurance Portability and Accountability Act (PL 104-191). Although limited, these provisions were instrumental in focusing national attention and debate on people's need for and right to behavioral health services. A handful of states have also passed parity provisions, but their full impact on the insurance market cannot be assessed. This is because a majority of plans are preempted from compliance with many state insurance mandates by the Employee Retirement Income Security Act of 1974 (ERISA). ERISA is the primary obstacle to state behavioral health mandates, and it threatens the inclusion of behavioral health providers and settings in managed care plans integrating public and private healthcare systems. This article provides basic information on ERISA, its preemption clauses, and its impact on behavioral healthcare services.

Career Mobility

A method to increase silver biosorption by an industrial strain of Saccharomyces cerevisiae.

Ag+ biosorption by an industrial strain of Saccharomyces cerevisiae was investigated. Older (96 h old) biomass had half the biosorption capacity of younger (24 h old) biomass (0.187 and 0.387 mmol Ag+/g dry mass respectively). Comparisons of cell walls isolated from biomass of either age indicated that chemical composition and Ag+ biosorption capacity varied little over the time span examined and that cell walls from either age of culture had small Ag+ biosorption capacities compared to whole cells of a similar age. Silver-containing precipitates were observed both on the cell wall and within the cell, indicating that intracellular components sorbed Ag+. The concentration of these precipitates within the cell appeared visually to decrease with age in Ag(+)-exposed cells. Incorporation of L-cysteine into the growth medium resulted in biomass with increased silver biosorption capacities, protein and sulphydryl group content. Increasing the concentration of L-cysteine in the growth medium from 0 to 5.0 mM increased silver biosorption from 0.389 to 0.556 mmol Ag+/g dry mass. Isolated cell walls of biomass grown in supplemented media also showed a possible link between silver biosorption capacities, protein and sulphydryl group content. No precipitates were observed in silver-exposed biomass that had been grown in the presence of 5.0 mM L-cysteine.

Adsorption

High-level expression of a novel epitope of CD59 identifies a subset of CD34+ bone marrow cells highly enriched for pluripotent stem cells.

To further define the hierarchy of human hematopoietic progenitor cells, we have attempted to identify antibodies to cell-surface molecules expressed on CD34+ progenitor cell subsets. Herein we describe the utility of a new monoclonal antibody, HCC-1, which binds to a novel epitope of CD59 differentially expressed among CD34+ progenitor cells. HCC-1 subdivides the adult marrow CD34+ population into HCC-1high and HCC-1low/- fractions of approximately equal size. Cobblestone area-forming cells (CAFC) in long-term bone marrow culture were enriched 10-30-fold in CD34+HCC-1high cells compared with CD34+HCC1-low/- cells and two-fold compared with CD34+ cells. When injected into fetal human bone fragments implanted in SCID mice, the CD34+HCC-1high population showed potent engrafting activity leading to the production of myeloid, lymphoid, and erythroid elements, as well as the retention of progenitor cell phenotype. These studies demonstrate that the CD34+HCC-1high population contains primitive pluripotent hematopoietic stem cells. No hematopoietic engrafting activity was detected in the CD34+HCC-1low/- population. Consistent with this finding, simultaneous five-color flow cytometric analysis revealed that HCC-1high cells include virtually all CD34+Thy-1+Lin- cells, a cell population previously characterized as highly enriched for primitive pluripotent hematopoietic stem cells. The ability of CD34+ cells divided into subsets by HCC-1 to produce T cells was assessed by transplantation of sorted cells into human fetal thymus implanted into SCID mice. A higher frequency of thymus-engrafting activity was observed in the CD34+HCC-1high than in the CD34+HCC-1low/- population. Consistent with the limited ability to engraft in the SCID-hu thymus model, the CD34+HCC-1low/- population was shown to contain a low frequency of CD34+CD10+ lymphoid progenitor cells. We conclude that the HCC-1 epitope is expressed at high levels on a subset of CD34+ cells that contain virtually all primitive pluripotent hematopoietic stem cells and that the population of CD59 molecules expressed on CD34+ cells is not homogeneous.

Animals

The transfer of signals from photoreceptor cells to large second-order neurones in the ocellar visual system of the locust Locusta migratoria

The operation of the first synapse in the ocellar pathway of the locust Locusta migratoria has been studied by making simultaneous intracellular recordings from photoreceptors and large, second-order L-neurones. 1. The transfer curve for the synapse, obtained by plotting the amplitudes of the initial peak responses by the two cells to pulses of light against each other, shows that L-neurones are extremely sensitive to changes in photoreceptor potential and that the connection is tonically active in darkness. 2. Postsynaptic current in an L-neurone, produced when pulses of light are delivered from a dark background, saturates at a slightly brighter light intensity than does the postsynaptic potential. 3. The signal-to-noise ratio improves with increases in light intensity in both cells, but the reduction in noise as signals are transmitted from photoreceptors to L-neurones is less than would be expected from the number of photoreceptors that probably converge on each L-neurone. 4. In both cells, in the presence of different intensities of background illumination, the slope of the intensity­response curve is maintained as the curve moves along the light intensity axis. Adaptation is relatively slow so that, at least for several minutes after an increase in background illumination, both cells maintain a sustained response and the responses to stimuli of increased illumination are reduced in amplitude. During sustained background illumination, the transfer curve for the synapse between a photoreceptor and an L-neurone shifts along both axes without a change in its maximum slope. 5. The slope of the synaptic transfer curve depends on the speed as well as the amplitude of changes in light. 6. In response to injection of depolarising pulses of current into a photoreceptor, an L-neurone generates brief, hyperpolarising responses. The amplitude of the responses depends on the strength and speed of the depolarising stimuli. After an initial response by an L-neurone, subsequent responses are reduced in amplitude for 200 ms. 7. The amplitude of L-neurone responses to electrical stimulation of a photoreceptor increases when the hyperpolarising constant current is injected into the photoreceptor.

Journal Article

Identification of homeobox genes expressed in human haemopoietic progenitor cells.

Homeodomain (HD)-containing proteins have been shown to regulate cellular commitment and differentiation in fungal, invertebrate and vertebrate systems. Bone marrow cells synthesizing the CD34 antigen are a complex mix of early, stem and progenitor cells at various stages of commitment to the many haemopoietic lineages. Here, we report the cloning and sequencing of 31 homeobox (HB) sequences, identified using degenerate oligodeoxyribonucleotide primers, in a polymerase chain reaction with cDNA derived from a purified CD34+ population of human haemopoietic cells. Of these sequences, 16 correspond to previously identified genes, and 13 are located within the HOX A, B and C clusters. Ten of the clones most likely represent human homologues of genes identified previously in other species. Five of the clones reported here represent novel HD sequences. The identification of five new genes using a subclass-specific 5' primer, designed from the engrailed and Xanf1 sequences, suggests that there still remain several uncharacterized HB genes in the human genome. Haemopoietic cells purified on the basis of CD34 antigen synthesis are a rich source of regulatory genes consistent with their ability to differentiate into diverse haemopoietic cell types.

Amino Acid Sequence

Trial of a topically administered local anesthetic (EMLA cream) for pain relief during central venous port accesses in children with cancer.

Procedure-related pain is a significant problem for many children receiving cytotoxic chemotherapy. In an effort to lessen this toxicity, we studied the efficacy and safety of administering topical local anesthesia using EMLA cream in 47 evaluable children with cancer undergoing implanted central venous port injections. Children (< 21 years old) scheduled to undergo repeated venous access procedures were selected for study. A placebo-controlled, randomized, double-blind, crossover study design was utilized. Statistically significant decreases in pain intensity scores (P < 0.002) were recorded by both children and investigators during the use of EMLA cream as compared with placebo. There was a good correlation between pain scores recorded by both patients and health care providers using both visual analog scales and categorized pain measurement tools. The topical application of EMLA cream 5% provides highly effective superficial anesthesia, and promises to be extremely useful for pain relief during percutaneous access procedures in cancer patients.

Administration, Cutaneous

CHARACTERISATION OF LARGE SECOND-ORDER OCELLAR NEURONES OF THE BLOWFLY CALLIPHORA ERYTHROCEPHALA

1. Blowflies have twelve large, second-order ocellar neurones (L-neurones) with axons in the single ocellar nerve. These neurones have fairly restricted arborizations in the posterior slope neuropile of the protocerebrum and cell bodies in the nerve, near to the fused ocellar retinae. 2. Like ocellar L-neurones of other insects, or large second-order neurones of the fly compound eye, blowfly L-neurones hyperpolarise in response to increases in light intensity and depolarise in response to decreases in light intensity. Both polarities of response have a strong phasic component. Adaptation to sustained illumination shifts the intensity&shy;response curve, with little change in its gradient. 3. The maximum responses of blowfly L-neurones to sinusoidal changes in light intensity occur at stimulus frequencies of 5&shy;10 Hz. 4. Hyperpolarising an L-neurone with small currents causes an increase in input resistance. Larger hyperpolarising currents cause oscillations in the membrane potential. The amplitude of the oscillations increases with current strength. Repolarisation generates brief rebound spikes of variable amplitude. 5. Injection of small hyperpolarising currents increases the amplitude of a response to a subsaturating pulse of light. This effect is not seen for saturating responses to light and is likely to be due to the increase in membrane resistance caused by hyperpolarisation.

Journal Article

A human interleukin 3 analog with increased biological and binding activities.

Human interleukin 3 (IL-3) variants generated by site-directed mutagenesis were analyzed in multiple biological and binding assays to identify residues critical for IL-3 activity. Two mutants carrying substitutions in the predicted hydrophilic region within the first alpha-helix, [Ala21,Leu22]IL-3 and [Ala21,Leu22,Ala25]IL-3 showed loss of biological activity and high-affinity binding. Mutants in a second predicted hydrophilic region, [Ala44,Leu45,Ala46]IL-3 and [Ala44,Ala46]IL-3, however, showed similar biological and binding activities to wild-type IL-3. Mutations in a C-terminal hydrophilic region that overlaps the fourth predicted alpha-helix led to either loss or gain of function. IL-3 analogs [Glu104,Asp105]-, [Leu108]-, [Asn108]-, [Thr108]-, and [Ala101,Leu108]IL-3 were less active than wild-type IL-3, whereas [Ala101]IL-3 and [Val116]IL-3 were 2- to 3-fold more potent. Significantly, the double mutant [Ala101,Val116]IL-3 exhibited a 15-fold greater potency than native IL-3. Receptor binding studies showed that [Ala101,Val116]IL-3 exhibited increased binding to the high- and low-affinity receptors of monocytes. These results show the generation of an IL-3 analog with increased biological and binding activities and support a model where the C terminus of IL-3 interacts with the alpha chain of the IL-3 receptor, making this region a useful focus for the development of more potent IL-3 agonists or antagonists.

Amino Acid Sequence

Cytomegalovirus and marrow function.

Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. A proportion of patients with CMV infection also experience neutropenia. To investigate the possible role of CMV in the suppression of hematopoiesis, we have examined the effect of CMV on the growth of isolated myeloid progenitors and on the production of myeloid cells in the long-term bone marrow culture (LTMC) system. In these studies, various isolates of CMV were added either directly to cultures of progenitors or to LTMC established from normal CMV-seronegative donors. In the first system, myelosuppression is manifested by a reduction in the number of colonies that grow. In the second system, myelosuppression is manifested by a reduction in the number of myeloid cells produced and released into the culture supernatant. Analysis of the data observed indicated that myelosuppression could in some cases be attributed to direct infection of myeloid progenitors. In other cases stromal cells were infected. In the latter cases, myelosuppression was then caused by an alteration in cytokines produced by the stromal cells. These observations made in vitro raise the possibility that comparable mechanisms may be responsible for the myelosuppression observed with CMV infection in vivo. To pursue this possibility we proposed to detect the CMV genome in defined subpopulations of marrow cells isolated from infected patients. Given the technical restrictions imposed by the small sample size available from patient marrow aspirations, our initial attempts to develop on appropriate technique involved isolation of cells from CMV-seropositive normal bone marrow donors. Using the polymerase chain reaction we were able to amplify CMV DNA contained within marrow cells of some healthy CMV-seropositive marrow donors.

Bone Marrow

Mechanisms of cytomegalovirus-mediated myelosuppression: perturbation of stromal cell function versus direct infection of myeloid cells.

Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. To study the role of CMV in the suppression of hemopoiesis that frequently accompanies infection, we investigated the effect of CMV on the growth of isolated committed myeloid progenitors and on hemopoiesis in long-term bone marrow cultures. Laboratory strain AD169 had no effect on the growth and development of progenitor cells. In contrast, 40% of clinical isolates of CMV inhibited colony formation by up to 100%. In long-term bone marrow cultures all CMV isolates resulted in myelosuppression, which in the majority of cases was associated with the infection of stromal elements. Analysis of RNA from stromal cells infected with AD169 and one clinical isolate demonstrated a specific deficiency of granulocyte colony-stimulating factor transcripts. For a small proportion of the clinical isolates tested in long-term bone marrow cultures, suppression of hemopoiesis was correlated with infection of developing granulocytes. These studies suggest that CMV can impair hemopoiesis either through infection of stromal cells and consequent perturbation of growth factor production or by direct infection of myeloid cells.

Antigens, Viral

A technique for spot application of fibrin glue during open heart operations.

Several techniques have been described for preparing and applying fibrin glue to control surgical bleeding. However, these methods tend to be cumbersome, expensive, or messy. Furthermore, commercial kits have not been approved by the Food and Drug Administration because of the potential risk of hepatitis contamination. Therefore, we have devised a modified, simpler technique that enables the precise, pinpoint application of fibrin glue. The risk of hepatitis transmission is substantially reduced by using cryoprecipitate plasma instead of fibrinogen from pooled donors. This technique is especially well suited for anastomoses of small vessels or for sealing suture holes in nonporous grafts.

Aprotinin

Quantitative evaluation of real-time ultrasound features of the breast.

Semi-quantitative diagnostic features were extracted by a visual analysis of the echographic images of selected cases of breast disease and the results stored in a computer database. The long term aim is to create an environment suitable for the use of multivariate statistical methods systematically to evaluate ultrasound interpretive criteria and diagnostic performance in relation to factors such as scanning instrumentation and other diagnostic techniques. Eventually it is hoped that it will be possible to generate a system for computer assisted diagnosis and training. The results of this pilot study serve to demonstrate the feasibility of the approach and a univariate analysis is used to provide a preliminary ranking of diagnostic features. Features found to be particularly valuable for distinguishing benign from malignant solid lesions were the regularity and definition of the edge of the tumour, the mobility of the tumour and measures of echo heterogeneity within and posterior to the tumour mass.

Breast