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Biomedical subjects

M Lacy

Publications and source records attributed to M Lacy.

16 recordsLinked to original sources
PubMed2001

Evaluating 2 year outcome in twins < or = 30 weeks gestation at birth: a regional perinatal unit's experience.

With improved technology in assisted reproductive medicine, there has been an absolute increase in the numbers of twin pregnancies with an associated increase in perinatal mortality and morbidity. This increase in perinatal mortality and morbidity is largely due to a higher incidence of delivering preterm as compared to singletons. Twin pregnancies have their unique complications that include abnormal placental communication and discordant growth which are associated with perinatal mortality and morbidity. The objectives of this study were two-fold: i) to determine if the morbidity/mortality outcome at 18-24 months corrected age seen in a cohort of twins born between 24-30 weeks gestation was significantly different as compared to singleton preterm infants of the same gestation; and ii) to determine and evaluate any differences between monochorionic (MC) and dichorionic (DC) twins. Twins 24-30 weeks gestation at birth born between 01/01/97-30/06/99 were identified and prospectively followed to 18-24 months corrected age (c.a.). They were matched with a singleton infant of the same gender and within 1 week of the same gestation. Obstetrical, neonatal and neurodevelopmental data were gathered and analyzed. The primary outcome was death or the presence of a severe neurodevelopmental deficit at 18-24 months corrected age. Of the 56 sets of twins identified, 52 sets were followed prospectively with 101 infants available for matching. In this cohort, twin pregnancies had a lower incidence of pregnancy-induced hypertension and premature rupture of membranes than singletons (p < 0.05). The two groups were comparable in neonatal characteristics. The incidence of death or severe disability was 29.7% in twins vs. 22.8% in singletons (p = 0.337, Fisher's exact test). The major area of defect was in the cognitive category for both groups, 9.9% vs. 7.9% respectively. MC twins made up 35.6%; DC twins 64.4%. Twin to twin transfusion syndrome (TTTS) occurred in 6.9%. Discordant growth occurred more frequently in MC pregnancies (p = 0.016). MC twins tended to be more premature, lower in birth weight, and experience neonatal morbidity in the form of patent ductus arteriosus and sepsis (p < 0.05) as compared to DC twins. However, the primary outcome of death or severe neurodevelopmental deficit at 18-24 months c.a. was not significantly different between the two groups, 38.9% (MC) vs. 24.6% (DC), (p = 0.173, Fisher's exact test). Neurodevelopmental morbidity or mortality in twins with TTTS was 42%. Mortality and severe neurodevelopmental morbidity were not signif cantly higher in twins as compared to singletons in this cohort. However, the trend is slightly higher in twins, which may have clinical significance. Though not statistically significant, the incidence of 38.9% in adverse outcome wth MC twins may be clinically significant. With the number of twins steadily increasing, further monitor ng is required to determine future directions in intervention and research. Early recognition of monochorionicity remains essential to optimize care and neurodevelopment for these infants.

Child Development↗
PubMed2000

Arabidopsis map kinase 4 negatively regulates systemic acquired resistance.

Transposon inactivation of Arabidopsis MAP kinase 4 produced the mpk4 mutant exhibiting constitutive systemic acquired resistance (SAR) including elevated salicylic acid (SA) levels, increased resistance to virulent pathogens, and constitutive pathogenesis-related gene expression shown by Northern and microarray hybridizations. MPK4 kinase activity is required to repress SAR, as an inactive MPK4 form failed to complement mpk4. Analysis of mpk4 expressing the SA hydroxylase NahG and of mpk4/npr1 double mutants indicated that SAR expression in mpk4 is dependent upon elevated SA levels but is independent of NPR1. PDF1.2 and THI2.1 gene induction by jasmonate was blocked in mpk4 expressing NahG, suggesting that MPK4 is required for jasmonic acid-responsive gene expression.

Alleles↗
PubMed2000

Radio Galaxy Clustering at z approximately 0.3.

Radio galaxies are uniquely useful as probes of large-scale structure since their uniform identification with giant elliptical galaxies out to high redshift means that the evolution of their bias factor can be predicted. As the initial stage in a project to study large-scale structure with radio galaxies, we have performed a small redshift survey, selecting 29 radio galaxies in the range of 0.19<z<0.45 from a contiguous 40 deg(2) area of sky. We detect significant clustering within this sample. The amplitude of the two-point correlation function that we measure is consistent with no evolution from the local (z<0.1) value. This is as expected in a model in which radio galaxy hosts form at high redshift and thereafter obey a continuity equation, although the signal-to-noise ratio of the detection is too low to rule out other models. Larger surveys out to z approximately 1 should reveal the structures of superclusters at intermediate redshifts and should strongly constrain models for the evolution of large-scale structure.

Journal Article↗
PubMed1999

Attitudes of veterinary medical students, house officers, clinical faculty, and staff toward pain management in animals.

OBJECTIVE: To determine whether animal factors and level of professional veterinary medical training were associated with attitudes toward pain management in animals. DESIGN: Exploratory, descriptive survey. SAMPLE POPULATION: Students in the College of Veterinary Medicine and Biomedical Sciences professional veterinary medical curriculum (approx 540) and clinical faculty (approx 50), house officers (approx 25), and support staff (approx 100) in the Colorado State University Veterinary Teaching Hospital. PROCEDURE: A descriptive survey including demographic, descriptive, and case-based questions was distributed to participants. Participation was voluntary and survey results were anonymous. RESULTS: 357 of 720 surveys were completed and returned (31 by faculty, 29 by staff, 18 by house officers, and 279 by students). There was a high degree of concordance among survey participants regarding the overall importance of treating pain in animals. The extent to which pain should be alleviated and animal factors, such as breed, behavior, and clinical circumstances, accounted for much of the discordance among survey groups. Fourth-year veterinary students indicated that they were occasionally less likely to treat animals for pain than were second- or third-year veterinary students. CLINICAL IMPLICATIONS: The diversity of opinions regarding the necessity or desirability of treating pain in animals, the apparent decrease in the likelihood of senior veterinary students to treat animals for pain under certain circumstances, and evidence of knowledge deficits regarding analgesic treatments among all groups contribute to the likelihood that pain in animals will neither be consistently recognized nor appropriately treated.

Analgesia↗
PubMed1999

Abnormal cytogenetics predict poor survival after high-dose therapy and autologous blood cell transplantation in multiple myeloma.

We compared the prognostic value of conventional cytogenetic analysis and established factors such as beta2-microglobulin and plasma cell labeling index in 70 patients undergoing autologous blood cell transplantation for multiple myeloma. Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Factors studied were age, sex, beta2-microglobulin, response to prior therapy, plasma cell labeling index, cytogenetic analysis, bone marrow plasma cell percentage, lactate dehydrogenase and C-reactive protein. Twenty-eight of 65 patients (43%) had abnormal marrow cytogenetics. Overall survival measured from transplantation was significantly better in patients with normal cytogenetics than in those with abnormal cytogenetics (median survival, 25 vs 12 months, P = 0.003). Progression-free survival was better, with median times of 12 vs7 months, respectively (P = 0.005); overall survival measured from the time myeloma was first diagnosed was also longer, with median survivals of 62 and 39 months, respectively (P = 0.001). Median plasma cell labeling index was 1.5% in patients with abnormal cytogenetics and 0. 2% in those with normal cytogenetics (P < 0.001). Abnormal bone marrow cytogenetics predict poor survival after blood cell transplantation for myeloma. There is a significant correlation between abnormal cytogenetics and high plasma cell labeling index, suggesting that certain cytogenetic abnormalities may offer a proliferative advantage to myeloma cells.

Adult↗
PubMed1998

Syndecan-1 is a multifunctional regulator of myeloma pathobiology: control of tumor cell survival, growth, and bone cell differentiation.

Multiple myeloma is characterized by an accumulation of malignant plasma cells in the bone marrow coupled with an altered balance of osteoclasts and osteoblasts, leading to lytic bone disease. Although some of the cytokines driving this process have been characterized, little is known about the negative regulators. We show that syndecan-1 (CD 138), a heparan sulfate proteoglycan, expressed on and actively shed from the surface of most myeloma cells, induces apoptosis and inhibits the growth of myeloma tumor cells and also mediates decreased osteoclast and increased osteoblast differentiation. The addition of intact purified syndecan-1 ectodomain (1 to 6 nmol/L) to myeloma cell lines in culture leads to induction of apoptosis and dose-dependent growth inhibition, with concurrent downregulation of cyclin D1. The addition of purified syndecan-1 in picomolar concentrations to bone marrow cells in culture leads to a dose-dependent decrease in osteoclastogenesis and a smaller increase in osteoblastogenesis. In contrast to the effect on myeloma cells, the effect of syndecan-1 on osteoclastogenesis only requires the syndecan-1 heparan sulfate chains and not the intact ectodomain, suggesting that syndecan's effect on myeloma and bone cells occurs through different mechanisms. When injected in severe combined immune deficient (scid) mice, control-transfected myeloma cells (ARH-77 cells) expressing little syndecan-1 readily form tumors, leading to hind limb paralysis and lytic bone disease. However, after the injection of syndecan-1-transfected ARH-77 cells, the development of disease-related morbidity and lytic bone disease is significantly inhibited. Taken together, our data demonstrate, both in vitro and in vivo, that syndecan-1 has a significant beneficial effect on the behavior of both myeloma and bone cells and therefore may represent one of the central molecules in the regulation of myeloma pathobiology.

Animals↗
PubMed1998

Photometry and spectroscopy of the GRB 970508 optical counterpart

An optical transient within the error box of the gamma ray burst GRB 970508 was imaged 4 hours after the event. It displayed a strong ultraviolet excess, and reached maximum brightness 2 days later. The optical spectra did not show any emission lines, and no variations on time scales of minutes were observed for 1 hour during the decline phase. According to the fireball and afterglow models, the intensity should rise monotonically before the observed optical maximum, but the data indicate that another physical mechanism may be responsible for the constant phase seen during the first hours after the burst.

Journal Article↗
PubMed1996

Generation and analysis of 280,000 human expressed sequence tags.

We report the generation of 319,311 single-pass sequencing reactions (known as expressed sequence tags, or ESTs) obtained from the 5' and 3' ends of 194,031 human cDNA clones. Our goal has been to obtain tag sequences from many different genes and to deposit these in the publicly accessible Data Base for Expressed Sequence Tags. Highly efficient automatic screening of the data allows deposition of the annotated sequences without delay. Sequences have been generated from 26 oligo(dT) primed directionally cloned libraries, of which 18 were normalized. The libraries were constructed using mRNA isolated from 17 different tissues representing three developmental states. Comparisons of a subset of our data with nonredundant human mRNA and protein data bases show that the ESTs represent many known sequences and contain many that are novel. Analysis of protein families using Hidden Markov Models confirms this observation and supports the contention that although normalization reduces significantly the relative abundance of redundant cDNA clones, it does not result in the complete removal of members of gene families.

Adult↗
PubMed1995

Expression of the receptors for the C5a anaphylatoxin, interleukin-8 and FMLP by human astrocytes and microglia.

The expression of chemotactic receptors in the central nervous system is largely unexplored. In this study, we examined human astrocytes and microglia as well as the conditionally immortalized human astrocyte cell line HSC2 for expression of the C5a-anaphylatoxin receptor (C5aR), the interleukin-8 receptor (IL-8R) and the f-Met-Leu-Phe receptor (FMLPR). Using flow cytometry, indirect immunofluorescence and RT-PCR analysis, we demonstrated that astrocytes, microglia and HSC2 cells contain specific RNA and express surface protein for all three chemotactic receptors. These are the first studies to demonstrate definitively the expression of these chemotactic receptors astrocytes and microglia, thereby expanding the types of cells known to express chemotactic receptors. Moreover, these data suggest that these chemotactic receptors may play an important role in mediating the inflammatory response and perhaps other yet undescribed biological phenomena in the central nervous system.

Adult↗
PubMed1990

Effects of apomorphine on novelty-induced place preference behavior in rats.

Adult male rats were exposed to one of two different stimulus compartments by being placed into the compartment for 30 min on each of eight consecutive days. Following this exposure, each rat was administered 0, 0.05, 0.1, 0.5 or 5.0 mg/kg apomorphine. Thirty min after injection, each animal was given free-choice access to the familiar (exposed) compartment and to the novel (nonexposed) compartment. As expected, saline-injected control animals displayed a preference for the novel compartment. This novelty preference was disrupted in animals given either 0.05 or 0.1 mg/kg apomorphine, but not in animals given either 0.5 or 5.0 mg/kg apomorphine. The disruption in novelty preference by the low doses of apomorphine did not reflect a disruption of locomotor activity, as there was no direct relationship between the preference for novelty and the rate of horizontal or vertical activity among the different treatment groups. Instead, the low doses of apomorphine may have inhibited dopamine function by blocking presynaptic autoreceptors selectively, and thus the reinforcing effect of the novel stimulation may have been attenuated.

Animals↗
PubMed1988

Degradative pathways in cultured synovial fibroblasts: selective effects of pulsed electromagnetic fields.

A cell culture model for studying the cytokine-mediated degradation of connective tissue was exposed to clinically applied, low-frequency pulsed electromagnetic fields (PEMF), and levels of collagenolytic activity, two lysosomal hydrolases, and prostaglandin E2 were measured. PEMFs reduced the release of two lysosomal enzymes by cultured rabbit synovial fibroblasts but did not affect their response to mononuclear-cell-conditioned medium. PEMF did not alter levels of cytokine activity produced by a mixed mononuclear cell population, nor did they affect the cytokine-mediated release of collagenase or prostaglandin E2 by synovial fibroblasts. The relevance of these findings to the clinical application of PEMF to soft- and hard-tissue injuries is discussed.

Acetylglucosaminidase↗
PubMed1988

A mammalian cell mutant with enhanced capacity to dissociate a bis-benzimidazole dye-DNA complex.

The bis-benzimidazole dyes (specifically Hoechst 33258 and the more lipophilic derivative Hoechst 33342) are non-intercalating AT base pair-specific ligands which bind to cellular DNA by non-covalent association with the minor groove. The interaction of dye with cellular DNA is thought to be the principal pathway for the cytotoxic, mutagenic and DNA-damaging properties of such agents. Upon binding and near UV light excitation, dye molecules exhibit fluorescence enhancement such that dye/DNA association and dissociation in individual cells can be monitored by flow cytometry. We have studied dye uptake and the DNA--dye dissociation characteristics of a Hoechst 33258-resistant mouse cell line (HoeR415) compared to the response of the parental cell line Ltk-. HoeR415 was found to show similar levels of cross resistance (approximately 10-fold) to Hoechst 33258 and Hoechst 33342 compared to parental responses except that the more lipophilic ligand was approximately 30-fold more toxic. Estimates of Hoechst 33342 uptake using flow cytometry or radiolabelling methods indicated that resistance could not be attributed to reduced cellular uptake, low initial levels or different modes of DNA binding. Both cell lines showed similar initial levels of dye-induced DNA strand-breakage. However, Hoechst 33342 resistance did correlate with an enhanced capacity (10-fold) of HoeR415 to remove dye from cellular DNA compared with the relatively long retention (T 1/2 300 min) of ligand by the parental cell line. Our results are consistent with the view that ligand persistence rather than indirect DNA damage is a more important factor in the cytotoxicity of non-intercalating DNA-binding ligands. A model is presented of the cellular processes of DNA damage recognition and surveillance for ligands which interact with the minor groove of DNA.

Animals↗
PubMed1985

An example of the use of quantitation in histological diagnosis by a comparison of normal human cheek mucosa and cheek mucosa affected by lichen planus.

As an example of the use of quantitation in histological diagnosis the features of normal human cheek mucosa (NHCM) and non-ulcerative lichen planus of the cheek mucosa (LPCM) have been systematically studied and quantified in order to establish normal and pathological features which are constant. The technique enabled the quantitative verification of previously held concepts relating to NHCM and LPCM. A number of interesting features which have been given little attention in past literature were also noted. It is proposed that a reliable quantifiable range of characteristic histological features should be established for use in diagnosis where possible rather than relying on the subjective approach currently employed.

Basement Membrane↗
PubMed1981

Creating a safe and supportive treatment environment.

The physical environment of a psychiatric facility can, by careful design, provide both a safe and supportive base for the treatment program. One requirement is an environment that is not monotonous; the lack of adequate stimuli leads to boredom, disorientation, and abnormal behavior. Visual stimuli are essential; they can come from changing patterns of light (preferably from the outdoors), variations in texture, colorful graphics, and variations in color value as well as in the colors themselves. Visual effects can also be used to improve the traditional long corridors, which foster alienation and disorientation, and to cause spaces to appear larger or smaller. Allowing patients some control over their environment, by encouraging them to hang personalized decorations, rearrange furniture, or participate in renovations, can relieve frustration and the sense of helplessness.

Environment Design↗
PubMedDate not supplied

Dendritic cell-based treatment of cancer: closing in on a cellular therapy.

PURPOSE: Dendritic cells are the most potent antigen-presenting cells and are critical to initiation of immune responses. Dendritic cells loaded ex vivo with tumor-associated antigen are being administered to cancer patients in an effort to jump-start a potent, cell-mediated anticancer immune response resulting in tumor shrinkage and clinical benefit. PATIENTS AND METHODS: Dendreon Corporation has designed three therapeutic vaccines using blood-derived dendritic cells loaded ex vivo with antigen: Provenge for prostate cancer; Mylovenge for multiple myeloma and other B-cell malignancies; and APC8024 for cancers expressing the HER-2/neu proto-oncogene. RESULTS: Preclinical studies demonstrated that blood dendritic cells matured spontaneously in short-term culture without growth factors, and that fusion of antigens with granulocyte-macrophage colony-stimulating factor enhances antigen uptake and presentation by blood dendritic cells. Phase I/II trials suggest that these dendritic cell-based vaccines are safe and well tolerated. Provenge has demonstrated antitumor activity in hormone-refractory prostate cancer; approximately 20% of patients experienced decreased prostate-specific antigen (i.e., PSA) levels and a similar percentage experienced disease stabilization. Double-blind, placebo-controlled, randomized trials in metastatic, asymptomatic hormone-refractory prostate cancer have been initiated. Phase II data on Mylovenge are similarly encouraging, and expanded phase II testing is ongoing in anticipation of opening phase III trials in 2002. APC8024 is in early clinical development and has shown significant capacity to elicit antigen-specific immune responses. CONCLUSION: Antigen delivery by ex vivo antigen-loaded dendritic cells may be an effective approach to cancer immunotherapy.

Cancer Vaccines↗