Biomedical subjects

M E Ross

Publications and source records attributed to M E Ross.

At least 55 records · Page 3Linked to original sources

PubMed1996

Myopia associated with hyperbaric oxygen therapy.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) involves exposing patients to elevated oxygen pressures and concentrations for the treatment of soft tissue degenerative diseases. As side effects, some patients experience cataract development and/or a significant increase in myopia. SUBJECTS: Eight subjects participated in this project. All were receiving HBOT for health problems. METHODS: For all subjects, acuities and refractive error corrections were measured before and after HBOT sessions at the beginning, midpoint, and end of therapy. For four subjects, A-scan ultrasound and corneal curvature measurements were also made before and after selected HBOT sessions. In addition, susceptibility to free radical damage and indicators of actual damage were measured by blood analyses. During the first half of HBOT therapy, four subjects took placebo tablets; during the second half, antioxidant supplements were given. RESULTS: No subject showed significant acuity or refractive error changes produced by single HBOT sessions. Two of the 8 subjects showed significant increases in myopia over the 20 session course of HBOT. No corresponding changes were found in the ultrasound, corneal curvature, or blood analysis data. DISCUSSION: Theoretically, the increases in myopia could have been caused by lenticular refractive index changes resulting from oxidative damage to lens proteins. However, the biochemical assays used in this project did not predict which subjects were susceptible to increased myopia, nor did they demonstrate elevated levels of free radical activity in a subject who did experience an increase in myopia.

Adult↗

PubMed1996

Aminoguanidine ameliorates and L-arginine worsens brain damage from intraluminal middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: We studied whether the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine reduces focal cerebral ischemic damage in a relatively noninvasive stroke model in which the rat middle cerebral artery (MCA) is occluded using an intravascular filament. METHODS: In rats anesthetized with halothane, a nylon filament was advanced into the internal carotid artery until its tip occluded the origin of the MCA. The filament was left in place for 2 hours and then withdrawn. Twenty-four hours later, rats received intraperitoneal injections of aminoguanidine (100 mg/kg BID; n = 7), aminoguanidine+L-arginine (300 mg/kg QID; n = 7), L-arginine alone (n = 6), D-arginine alone (n = 6), or vehicle (n = 10). Drugs were administered for 3 consecutive days. Infarct volume was determined by image analysis in thionin-stained brain sections 4 days after ischemia. iNOS mRNA was detected with the use of reverse transcription polymerase chain reaction. RESULTS: Cerebral ischemia led to iNOS mRNA expression in the affected brain 48 hours after induction of ischemia. Administration of aminoguanidine reduced neocortical infarct volume by 26% (P < .05 versus vehicle, ANOVA and Tukey's test), a reduction that was antagonized by coadministration of L-arginine (P > .05 versus vehicle). Administration of L-arginine alone, but not D-arginine, enlarged the infarct by 29% (P < .05). Aminoguanidine or L-arginine did not influence the increase in water content in the postischemic brain, indicating that the effect on infarct volume is not related to modulation of ischemic edema. CONCLUSIONS: These results demonstrate that cerebral ischemia is also associated with iNOS expression in a minimally invasive model of transient MCA occlusion and that iNOS inhibition reduces focal ischemic damage. The findings support the hypothesis that nitric oxide produced by iNOS contributes to ischemic brain damage and that inhibition of iNOS may be a valuable tool in the management of cerebral ischemia.

Animals↗

PubMed1996

Inducible nitric oxide synthase gene expression in vascular cells after transient focal cerebral ischemia.

BACKGROUND AND PURPOSE: We investigated whether inducible nitric oxide synthase (iNOS) is expressed after transient cerebral ischemia and, if so, we sought to define the temporal profile and cellular localization of the expression and the role of iNOS in the mechanism of ischemic brain injury. METHODS: The middle cerebral artery in rats was occluded for 2 hours by an intraluminal filament. The occurrence of transient ischemia and reperfusion was confirmed by laser-Doppler flowmetry (n = 5). iNOS message in the ischemic neocortex was determined by reverse-transcription polymerase chain reaction. iNOS enzymatic activity was assessed by citrulline assay. The cellular localization of iNOS expression was determined by immunohistochemistry. RESULTS: iNOS mRNA was maximally expressed in postischemic brain at 12 hours and was not present at 4 days (n = 3 per time point). iNOS mRNA was not observed in the contralateral cerebral cortex. iNOS enzymatic activity developed in the postischemic brain between 12 and 24 hours (P < .05) and subsided at 4 days (n = 4 to 8 per time point). iNOS immunoreactivity in the ischemic region was restricted to the wall of capillaries and of larger blood vessels at 12 to 24 hours. In regions of early necrosis, inflammatory cells were iNOS positive. Treatment with the iNOS inhibitor aminoguanidine (n = 5; 100 mg/kg IP, BID for 4 days), starting 6 hours after ischemia, reduced infarct size in neocortex by 36 +/- 7% in comparison with vehicle-treated controls (n = 5) (P < .05). CONCLUSIONS: Transient focal ischemia leads to iNOS expression in postischemic brain. However, the spatial and temporal patterns of expression differ from those occurring in permanent ischemia: iNOS is induced earlier and predominantly in vascular cells rather than in neutrophils. Thus, the temporal profile and localization of postischemic iNOS expression depend on the nature of the ischemic insult. The finding that aminoguanidine reduces infarct size adds further support to the hypothesis that postischemic iNOS expression contributes to ischemic brain damage.

Animals↗

PubMed1996

Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma.

PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.

Acquired Immunodeficiency Syndrome↗

PubMed1996

X-linked malformations of neuronal migration.

Malformations of neuronal migration such as lissencephaly (agyria-pachygyria spectrum) are well-known causes of mental retardation and epilepsy that are often genetic. For example, isolated lissencephaly sequence and Miller-Dieker syndrome are caused by deletions involving a lissencephaly gene in chromosome 17p13.3, while many other malformation syndromes have autosomal recessive inheritance. In this paper, we review evidence supporting the existence of two distinct X-linked malformations of neuronal migration. X-linked lissencephaly and subcortical band heterotopia (XLIS) presents with sporadic or familial mental retardation and epilepsy. The brain malformation varies from classical lissencephaly, which is observed in males, to subcortical band heterotopia, which is observed primarily in females. The XLIS gene is located in chromosome Xq22.3 based on the breakpoint of an X-autosomal translocation. Bilateral periventricular nodular heterotopia (BPNH) usually presents with sporadic or familial epilepsy with normal intelligence, primarily in females, although we have evaluated two boys with BPNH and severe mental retardation. The gene for BPNH has been mapped to chromosome Xq28 based on linkage studies in multiplex families and observation of a subtle structural abnormality in one of the boys with BPNH and severe mental retardation.

Adult↗

PubMed1996

MN20, a D2 cyclin, is transiently expressed in selected neural populations during embryogenesis.

Although the regulation of proliferation and differentiation during brain development has long been considered to be interrelated, the mechanisms that coordinate the control of cell division and histogenesis are poorly understood. The cell cycle is a dynamic process that is governed by the concerted action of numerous cell cycle regulatory proteins in response to signals both intrinsic and extrinsic to the cell. Thus, proteins that regulate the cell cycle are well suited to provide a link between processes that control neuroblast proliferation and differentiation. We reported previously the isolation from brain of a message form of D2 cyclin, one of several cyclin proteins known to promote the progression from G1 to S phase. This MN20/D2 cyclin mRNA is expressed in highly restricted neural populations at embryonic (E) day 15 and postnatal (P) day 6 in the mouse. To gain insight into the role(s) this cyclin may serve in brain formation, the spatial and temporal pattern of MN20/D2 cyclin expression was examined by in situ hybridization at 48 hr intervals from E10.5 to P8. MN20 mRNA was detected in developing cerebellum, dorsal mesencephalon, cerebral cortex, and epithalamus, but not hippocampus, striatum, or thalamus. Comparison with 5-bromodeoxyuridine labeling of cells in S phase indicated that MN20 expression in embryonic cerebellum and cerebral cortex was most pronounced in young neurons that recently had become postmitotic. Although expressed in other embryonic cerebellar neurons, MN20 was detected in granule precursors only postnatally, after their migration from the rhombic lip to the external germinal layer. This indicates that MN20/D2 cyclin is induced in cerebellar granule precursors as they become competent to differentiate. The spatial distribution of MN20 expression in the developing brain suggests that regional differences in cell cycle regulation depend in part on the selective use of cyclin proteins. Moreover, detection of MN20 mRNA in postmitotic neural cells indicates that cyclin D2 expression has effects beyond promoting cell cycle progression and may also have a role in the response of the neural precursor to terminal differentiation signals as the cells exits from proliferation.

Animals↗

PubMed1995

Regulation of PNMT gene promoter constructs transfected into the TE 671 human medulloblastoma cell line.

The human medulloblastoma TE 671 cell line has been evaluated as a model for studying expression of transiently transfected phenylethanolamine N-methyltransferase (PNMT) promoter-fusion gene constructs. Because TE 671 cells are one of few continuous lines exhibiting a neuronal phenotype, possess both nicotinic and muscarinic ligand binding properties, and express PNMT mRNA, they represent a likely candidate system for study of cholinergic-regulated PNMT gene expression. When transfected with constructs containing from 0.1 to 3 kb of the region 5' to the initiation site for PNMT gene transcription, TE 671 cells express at detectable levels only those constructs containing the -391 to -863 bp portion of the rat PNMT promoter fused to the chloramphenicol acetyltransferase (CAT) gene. Both general and selective cholinergic agents regulate expression of the -863 to -391 bp PNMT region in a TK promoter-CAT reporter construct. With this construct, carbachol stimulates CAT expression 1.5-fold in transfected TE 671 cells. The selective agonists nicotine and muscarine each stimulate expression of the upstream TK-CAT constructs 2.8- and 1.9-fold respectively, while antagonists for these receptors block induction. Because TE 671 cells respond to both nicotinic and muscarinic stimuli, this continuous line represents a useful model system for studying PNMT gene regulation by cholinergic stimuli.

Animals↗

PubMed1995

Lymphomagenesis in the SCID-hu mouse involves abundant production of human interleukin-10.

Both human (hu) and viral (v) interleukin-10 (IL-10) appear to be important cofactors in the survival and growth of lymphoblastoid cell lines infected with Epstein-Barr virus (EBV). When mice with severe combined immune deficiency (SCID) are injected with human peripheral blood lymphocytes (PBL) from normal individuals who are seropositive for EBV, the majority of hu-PBL-SCID mice will develop an EBV-associated lymphoproliferative disease (EBV-LPD) of human B-cell origin, not unlike some cases of EBV-LPD that are seen in immunocompromised individuals. The role of huIL-10 or vIL-10 in this chimeric mouse model of EBV-LPD is unknown. In the present study, we show that hu-PBL-SCID mice that develop EBV-LPD have significant elevation of serum huIL-10 levels compared with mice that do not develop EBV-LPD (P = .005). vIL-10 was undetectable in all animals. The EBV+ tumor samples express transcript for huIL-10 and huIL-10 receptor, express huIL-10 protein by immunohistochemical staining, and show specific binding of recombinant (r) huIL-10. In vitro analysis of the functional consequences of rhuIL-10 binding to IL-10 receptors on fresh EBV+ tumor cells shows that rhuIL-10 can prevent programmed cell death as well as promote proliferation and can do so at concentrations of huIL-10 found in vivo. Thus, huIL-10 production by EBV+ tumor cells may contribute directly to their malignant outgrowth in the hu-PBL-SCID mouse by two autocrine mechanisms: prevention of programmed cell death and proliferation. The implications of such findings with regard to EBV-LPD in humans is discussed.

Animals↗

PubMed1995

Inducible nitric oxide synthase gene expression in brain following cerebral ischemia.

Cerebral ischemia is followed by a local inflammatory response that is thought to participate in the extension of the tissue damage occurring in the postischemic period. However, the mechanisms whereby the inflammation contributes to the progression of the damage have not been fully elucidated. In models of inflammation, expression of the inducible isoform of nitric oxide synthase (iNOS) is responsible for cytotoxicity through the production of large amounts of nitric oxide (NO). In this study, therefore, we sought to establish whether iNOS is expressed in the ischemic brain. Rats were killed 6 h to 7 days after occlusion of the middle cerebral artery. iNOS expression in the ischemic area was determined by reverse-transcription polymerase chain reaction. Porphobilinogen deaminase mRNA was detected in the same sample and used for normalization. In the ischemic brain, there was expression of iNOS mRNA that began at 12 h, peaked at 48 h, and returned to baseline at 7 days (n = 3/time point). iNOS mRNA expression paralleled the time course of induction of iNOS catalytic activity, determined by the citrulline assay (17.4 +/- 4.4 pmol citrulline/micrograms protein/min at 48 h; mean +/- SD; n = 5 per time point). iNOS immunoreactivity was seen in neutrophils at 48-96 h after ischemia. The data provide molecular, biochemical, and immunocytochemical evidence of iNOS induction following focal cerebral ischemia. These findings, in concert with our recent demonstration that inhibition of iNOS reduces infarct volume in the same stroke model, indicate that NO production may play an important pathogenic role in the progression of the tissue damage that follows cerebral ischemia.

Amino Acid Oxidoreductases↗

PubMed1995

Marked induction of calcium-independent nitric oxide synthase activity after focal cerebral ischemia.

We studied the effect of focal cerebral ischemia on inducible (iNOS) and constitutive (cNOS) nitric oxide synthase enzymatic activities in the affected brain. The middle cerebral artery (MCA) was occluded in spontaneously hypertensive rats. Animals were killed 1, 2, 4, and 7 days later. cNOS and iNOS enzymatic activities were determined in the infarcted cortex using the assay of Bredt and Snyder. cNOS was assayed in the presence of calcium, whereas iNOS was assayed in the absence of calcium and in the presence of tetrahydrobiopterin. The validity of the iNOS assay was verified in rats treated with bacterial lipopolysaccharide. In these animals, the magnitude of the induction of iNOS enzymatic activity in lung, spleen, and brain paralleled the expression of iNOS mRNA, assessed by reverse-transcription polymerase chain reaction. After MCA occlusion, calcium-dependent (cNOS) activity was markedly reduced only in lesioned cerebral cortex at days 1-7 (p < 0.001; analysis of variance and Tukey's test). In contrast to cNOS, calcium-independent (iNOS) activity was induced substantially in the infarct (p < 0.005) but not in the contralateral intact cortex (p > 0.05). iNOS activity peaked at day 2 and was not different from baseline at day 7 (p > 0.05). No NADPH diaphorase-positive neurons were observed in the area of the lesion at days 1-7. Macrophages appeared at day 2 and invaded the infarcted tissue by day 7. At this time, numerous glial fibrillary acidic protein-positive astrocytes were observed within the lesion. The results suggest that the decline in calcium-dependent (cNOS) activity reflects loss of NOS neurons within the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1995

Endogenous production of interleukin 15 by activated human monocytes is critical for optimal production of interferon-gamma by natural killer cells in vitro.

Natural killer (NK) cells are large granular lymphocytes that constitutively express functional IL-2 receptors. We have shown that recombinant human IL-15 uses the IL-2 receptor to activate human NK cells and can synergize with recombinant human IL-12 to stimulate NK cell production of IFN-gamma in vitro. IFN-gamma production by NK cells is critical in the prevention of overwhelming infection by obligate intracellular microbial pathogens in several experimental animal models. Herein, we demonstrate that human monocytes produce IL-15 protein within 5 h of activation with LPS. Using an IL-15-neutralizing antiserum in a coculture of LPS-activated monocytes and NK cells, we demonstrate that monocyte-derived IL-15 is critical for optimal NK cell production of IFN-gamma. Endogenous IL-15 activates NK cells through the IL-2 receptor, and with endogenous IL-12, regulates NK cell IFN-gamma after monocyte activation by LPS. These in vitro studies are the first to characterize a function for endogenous IL-15, and as such, suggest an important role for IL-15 during the innate immune response. IL-15 may be an important ligand for the NK cell IL-2 receptor in vivo.

Animals↗

PubMed1995

Phase I/II clinical and pharmacokinetic evaluation of liposomal daunorubicin.

PURPOSE: Since liposomal encapsulation of anticancer drugs may enhance antitumor activity while reducing toxicity in vitro, we evaluated liposomally encapsulated daunorubucin (DaunoXome; Vestar, Inc, San Dimas, CA) for safety, pharmacokinetics, and potential efficacy in patients with AIDS-related Kaposi's sarcoma (AIDS-KS). PATIENTS AND METHODS: Forty patients with advanced AIDS-KS were accrued. Successive cohorts received DaunoXome at doses of 10, 20, 30, and 40 mg/m2 given once every 3 weeks, and 40, 50, and 60 mg/m2 given once every 2 weeks. Selected KS and solid-tumor patients underwent pharmacokinetic evaluation. RESULTS: The area under the plasma concentration curve (AUC) ranged from 16.9 micrograms.h/mL to 375.3 micrograms./mL and the alpha half-life ranged from 7.8 to 8.3 hours at 10 mg/m2 to 60 mg/m2, respectively. Both pharmacokinetic profiles were significantly better compared with free daunorubicin. DaunoXome was well tolerated with no significant alopecia, mucositis, or vomiting. Neutropenia (< 1,000/microL occurred in 17% of cycles and was severe (< 500/microL) in only 2%. Anemia and thrombocytopenia were uncommon. Other adverse events included mild to moderate fatigue, nausea, and diarrhea. Even after cumulative doses greater than 1,000 mg/m2, no significant declines in cardiac function were observed. Twenty-two patients who received 50 and 60 mg/m2 were assessable for tumor response; 12 (55%) had a partial response (PR) or clinical complete response (CR). The median survival duration in all patients was 9 months. Prognostic factors for short survival were low CD4 lymphocyte counts (P = .004) and prior anthracycline therapy (P = .02). CONCLUSION: DaunoXome has an improved pharmacokinetic profile compared with free daunorubicin, and is well tolerated. DaunoXome can be given safely at doses up to 60 mg/m2 every 2 weeks and has significant antitumor activity in patients with AIDS-KS.

Acquired Immunodeficiency Syndrome↗

PubMed1994

MN20, a D2 cyclin found in brain, is implicated in neural differentiation.

Cyclins are regulatory proteins that promote the progression of dividing cells through the cell cycle. D-type cyclins are important mediators of the transition from G1 into S phase of the cell cycle and are thought to be widely expressed in mitotically active tissues (Matsushime et al., 1991b; Inaba et al., 1992; Xiong et al., 1992). We report the isolation of a cDNA clone, MN20, which represents a D2 cyclin message form whose expression pattern is highly restricted to brain. MN20 is not ubiquitous, but rather it is expressed only in restricted neuronal precursor populations, for example, in proliferating granule neuroblasts of the cerebellum but not hippocampus. Strikingly, MN20 expression is also found in postmitotic neuronal precursor cells of the embryonic cerebral cortex, but not in the dividing cortical neuroblasts. These observations suggest that the D2 cyclin gene serves regionally specific functions in neuronal differentiation, some of which may be distinct from the promotion of cell cycle progression and which act at the interface between mitosis and the assumption of mature neuronal morphology.

Animals↗

PubMed1993

In vitro cytotoxicity of hepsulfam against human tumor cell lines and primary human tumor colony forming units.

Hepsulfam (sulfamic acid 1,7-heptanediyl ester, NSC 329680) is an alkylating agent currently in Phase I clinical trials. Hepsulfam was developed as an analog of busulfan, an alkylating agent that is used to treat patients with chronic myelogenous leukemia and for marrow ablation prior to bone marrow transplantation. The objective of this study was to identify the spectrum of human tumor cells that were sensitive to hepsulfam. The following three cytotoxicity assays were employed to evaluate the in vitro cytotoxic potential of hepsulfam: 1) primary human tumors were exposed to three levels of hepsulfam for a one hour or continuous exposure, and growth in soft agar was determined; 2) human non-tumor cells and tumor cell lines were compared in an assay that measured the conversion of 14C-glucose to 14CO2 as an index of viability; and 3) the toxicity of hepsulfam to hematopoietic progenitor cells was determined in a progenitor cell colony forming assay. Cytotoxicity was not observed for human tumor cells following one hour hepsulfam exposures; in contrast, marked dose-dependent cytotoxicity was observed with continuous exposures. In human tumor cell lines, the cytotoxicity of hepsulfam was compared directly with busulfan at equimolar concentrations. Hepsulfam was more cytotoxic than busulfan in all cell lines tested. Cytotoxic activity was seen in lung, melanoma, kidney, breast, colon, ovary and brain tumor cells. These results, along with the information obtained from Phase I trials, will facilitate selection of patients who could receive this agent in Phase II efficacy trials.

Antineoplastic Agents↗

PubMed1993

Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2.

The immunologic consequences of prolonged infusions of rIL-2 in doses that produce physiologic serum concentrations of this cytokine were investigated. rIL-2 in doses of 0.5-6.0 x 10(6) U/m2 per d (3.3-40 micrograms/m2 per d) was administered by continuous intravenous infusion for 90 consecutive days to patients with advanced cancer. IL-2 concentrations (25 +/- 25 and 77 +/- 64 pM, respectively) that selectively saturate high-affinity IL-2 receptors (IL-2R) were achieved in the serum of patients receiving rIL-2 infusions of 10 micrograms/m2 per d and 30 micrograms/m2 per d. A gradual, progressive expansion of natural killer (NK) cells was seen in the peripheral blood of these patients with no evidence of a plateau effect during the 3 mo of therapy. A preferential expansion of CD56bright NK cells was consistently evident. NK cytotoxicity against tumor targets was only slightly enhanced at these dose levels. However, brief incubation of these expanded NK cells with IL-2 in vitro induced potent lysis of NK-sensitive, NK-resistant, and antibody-coated targets. Infusions of rIL-2 at 40 micrograms/m2 per d produced serum IL-2 levels (345 +/- 381 pM) sufficient to engage intermediate affinity IL-2R p75, which is constitutively expressed by human NK cells. This did not result in greater NK cell expansion compared to the lower dose levels, but did produce in vivo activation of NK cytotoxicity, as evidenced by lysis of NK-resistant targets. There was no consistent change in the numbers of CD56- CD3+ T cells, CD56+ CD3+ MHC-unrestricted T cells, or B cells during infusions of rIL-2 at any of the dosages used. This study demonstrates that prolonged infusions of rIL-2 in doses that saturate only high affinity IL-2R can selectively expand human NK cells for an extended period of time with only minimal toxicity. Further activation of NK cytolytic activity can also be achieved in vivo, but it requires concentrations of IL-2 that bind intermediate affinity IL-2R p75. Clinical trials are underway attempting to exploit the differing effects of various concentrations of IL-2 on human NK cells in vivo.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1993

Linking ethical principles with community practice.

Nurses must frequently make arduous decisions when faced with ethical dilemmas that occur in clinical practice. Utilizing ethical principles for analyzing and reflecting on the issues may ease this difficult task. In addition, the nurse involved may experience less anxiety and uncertainty over whether or not the correct decision was made. The purpose of this article is to present a case study that involves the allocation of a scarce resource that posed an ethical dilemma for a nursing instructor and her students in a community health setting. Toulmin's framework is utilized for analyzing this dilemma.

Beneficence↗

PubMed1993

Changing patterns of gene expression define four stages of cerebellar granule neuron differentiation.

Among CNS neuronal populations, the cerebellar granule cell provides a simple model for analysing the molecular regulation of CNS neurogenesis. In this study, polyclonal antisera raised against immature granule cell precursors, purified from early postnatal mouse cerebellum, were used to isolate 39 unique cDNA clones from a lambda gt11 cDNA expression library made from the same cell population. Northern blot analysis revealed developmental stage and tissue-specific expression of 28 of the clones. In situ localization of mRNAs encoded by these novel cDNAs, as well as those encoding the axonal glycoprotein TAG-1 and the alpha 6 subunit of the GABAA receptor, reveal four distinct stages in cerebellar granule cell differentiation. The developmentally transient and spatially restricted expression of clones GC9 and GC44 identify a previously unrecognized step in cerebellar histogenesis.

Animals↗

PubMed1992

Selection of licensing candidates in the pharmaceutical industry: an application of the analytic hierarchy process.

The ethical (prescription) pharmaceutical industry depends on a stream of innovative, patent-protected products to maintain growth and profitability. With Sterling Drug's entry into a new therapeutic area (oncology, the study and treatment of cancer), licensing and research collaborations have become an important part of the process of developing a pipeline of potential new drugs. The application of the analytic hierarchy process has led to improved articulation of the relevant criteria and better definition of organizational procedures, thereby benefiting Sterling's decision-making process.

Data Collection↗