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Biomedical subjects

L Morse

Publications and source records attributed to L Morse.

14 recordsLinked to original sources
PubMed2001

Density-dependent expression of FGF-2 in response to oxidative stress in RPE cells in vitro.

PURPOSE: The purpose of this study is to demonstrate the effect of culture density on the steady state mRNA levels of fibroblast growth factor-2 (FGF-2) when retinal pigment epithelial (RPE) cells are subjected to oxidative stress in vitro. METHODS: Subconfluent and confluent cultures of the established RPE cell line ARPE-19, were treated with increasing concentrations of tert-butyl hydroperoxide (tBH) or hydrogen peroxide (H(2)O(2)). Cell viability was measured using the WST-1 assay, and intracellular reactive oxygen intermediate (ROI) production was quantified by dichlorofluoroscein (DCF) fluorescence. Steady state changes in heme oxygenase-1 (HO-1) and FGF-2 mRNAs were measured by Northern blot analysis. RESULTS: Confluent cultures of ARPE-19 cells were less susceptible than subconfluent cultures to the toxic effects of the chemical oxidants. The intracellular reactive oxygen intermediate production was higher in subconfluent than confluent cultures with increasing tBH concentration. At nontoxic concentrations of tBH and H(2)O(2), a dose dependent increase in FGF-2 expression was seen as a function of culture density. FGF-2 mRNA expression was induced after tBH treatment in subconfluent, but not confluent cells. On the other hand, FGF-2 mRNA induction was observed after H(2)O( 2) treatment in confluent, but not subconfluent cultures. In contrast, no density dependent induction of HO-1 mRNA was seen after treatment with either tBH or H(2)O(2). CONCLUSIONS: These results suggest that care should be taken to control for cell density in similar types of in vitro experiments.

Blotting, Northern↗
PubMed2000

A full genome scan for age-related maculopathy.

Age-related macular degeneration or age-related maculopathy (ARM) is a major public health issue, as it is the leading cause of irreversible vision loss in the elderly in the Western world. Using three diagnostic models, we have genotyped markers in 16 plausible candidate regions and have carried out a genome-wide screen for ARM susceptibility loci. A panel of 225 ARM families comprising up to 212 affected sib pairs was genotyped for 386 markers. Under our most stringent diagnostic model, the regions with the strongest evidence of linkage were on chromosome 9 near D9S301 and on 10 near D10S1230, with peak multipoint heterogeneity LOD scores (HLOD) of 1.87 and 1. 42 and peak GeneHunter-Plus non-parametric LOD scores (GHP LOD) of 1. 69 and 1.83. After expanding our initial set of families to 364 ARM families with up to 329 affected sib pairs, the linkage signal on chromosome 9 vanished, while the chromosome 10 signal decreased to a GHP LOD of about 1.0, with a SimIBD P -value of 0.008 under the broadest diagnostic model with marker D10S1236. After error filtration, the GHP LOD increased to 1.27 under our most stringent model and 1.42 under our broadest model, peaking near D10S1236. This peak was seen consistently across all three diagnostic models. Our analyses also excluded up to nine different candidate regions and identified a few other regions of potential linkage, suitable for further studies. Of particular interest was the region on chromosome 5 near D5S1480, where a reasonable candidate gene, glutathione peroxidase 3, resides.

Chromosomes, Human, Pair 10↗
PubMed2000

Fast-track cardiac anesthesia: use of remifentanil combined with intrathecal morphine as an alternative to sufentanil during desflurane anesthesia.

UNLABELLED: The purpose of this cardiac fast-track study was to evaluate the use of remifentanil (R) combined with intrathecal (IT) morphine as an alternative to sufentanil (S) during desflurane anesthesia with respect to postoperative pain control. Prior to entering the operating room, patients in the R group (n = 20) received morphine, 8 microg/kg IT. Anesthesia was induced using a standardized anesthetic technique in all patients. In the R group, anesthesia was maintained with R, 0.1 microg. kg(-1). min(-1) in combination with desflurane 3-10%. In the S group (n = 20), patients received S 0.3 microg. kg(-1). h(-1) and desflurane 3-10%. There were no differences between the two groups with respect to time from arrival in the intensive care unit to tracheal extubation (5.1 +/- 4.3 h vs 5.8 +/- 6.7 h for R and S groups, respectively). After extubation, patients in the R group had significantly lower visual analog pain scores, reduced patient-controlled analgesic requirements, and greater satisfaction with their perioperative pain management, compared with patients in the S group. We conclude that R combined with IT morphine provided superior pain control after cardiac surgery compared with a S-based general anesthetic technique. IMPLICATIONS: As part of a cardiac fast-tracking program involving desflurane anesthesia, the use of intrathecal morphine in combination with a remifentanil infusion provided improved postoperative pain control, compared with IV sufentanil alone.

Analgesics, Opioid↗
PubMed1997

Induction of cell cycle arrest and B cell terminal differentiation by CDK inhibitor p18(INK4c) and IL-6.

Cell cycle arrest and cell death are tightly coupled to terminal differentiation of B cells to plasma cells in vivo. This process was recapitulated in vitro by stimulation of IgG-bearing human B lymphoblastoid cells with interleukin-6 (IL-6), which led to orderly cell cycle arrest, differentiation, and apoptosis. In terminally differentiated plasmacytoid cells, phosphorylation of pRb was suppressed, correlating with the activation of the D-type cyclin-dependent kinase (CDK) inhibitors p18(INK4c) and p21(WAF1/CIP1). The expression of CDK6, however, remained unchanged. Activation of p18 by IL-6 was rapid, concomitant with marked enhancement of its association with CDK6 and cell cycle arrest. Overexpression of p18 in IgM-bearing lymphoblastoid cells, which differentiated in response to IL-6 but did not exit the cell cycle, reconstituted coupled differentiation and cell cycle arrest. Thus, CDK inhibitors, in particular p18, are likely to play a pivotal role in controlling cell cycle arrest and cell death in terminal differentiation of late-stage B cells to plasma cells via inhibition of pRb phosphorylation by CDK6.

Apoptosis↗
PubMed1994

Chemosensitivity of lymphocytes from patients with B-cell chronic lymphocytic leukemia to chlorambucil, fludarabine, and camptothecin analogs.

Chemosensitivity of B lymphocytes, obtained from 65 patients with B-cell chronic lymphocytic leukemia (B-CLL), Rai stages 0 through IV, was determined using the MTT assay. The results were expressed by the drug concentration required for 50% inhibition of cell viability (IC50). The cytotoxicity of chlorambucil (CLB) was compared with that of fludarabine and the DNA topoisomerase I inhibitors, camptothecin, 9-aminocamptothecin, 10,11-methylenedioxy-20(S)-camptothecin (10,11-MDC) and 9-amino-10,11-methylenedioxy-20(S)-campthothecin (9-A-10,11-MDC), and topotecan. Considerable heterogeneity in sensitivity to CLB was observed, with a median IC50 of 40.5 mumol/L in untreated patients. B-CLL cells from patients treated with CLB had a significantly higher median IC50 of 86.0 mumol/L (P < .01). Untreated as well as CLB-treated patients were divided into two subsets. For the purpose of this study, B-CLL lymphocytes with an IC50 CLB of less than 61.0 mumol/L were designated as "sensitive" and those with an IC50 CLB of > or = 61.0 mumol/L were designated as "resistant." After baseline assays, 15 untreated patients received CLB; after treatment, the IC50 increased in B-CLL lymphocytes from 13 of 15 patients. The response to CLB treatment, determined by its effect on the absolute lymphocyte count and by the Eastern Cooperative Oncology Group clinical criteria, was significantly better in patients whose lymphocytes had an IC50 CLB of less than 61.0 mumol/L before therapy (P < .01). B-CLL lymphocytes also had a variable degree of sensitivity in vitro to each of the other drugs. There was significant cross-resistance between CLB and fludarabine (P < 0.01). Whereas only 29% of CLB-resistant B-lymphocyte specimens obtained from individual patients were sensitive to fludarabine in vitro, 52% and 67% of CLB-resistant lymphocyte samples were sensitive to 10,11-MDC and 9-A-10,11-MDC, respectively. We have previously reported that p53 gene mutations were associated with aggressive B-CLL and a poor prognosis. B lymphocytes from seven patients with these mutations were resistant to CLB, and five of six were resistant to fludarabine. Lymphocytes from four of seven were resistant to 10,11-MDC, and three of four were resistant to 9-A-10,11-MDC. This study implies that the MTT assay may be useful in identifying subsets of CLL patients resistant to conventional chemotherapy. However, definitive conclusions can not be drawn in view of the small number of patients studied prospectively. In addition, these results suggest the potential of camptothecin-based therapy for patients unresponsive to standard treatment.

Antineoplastic Agents↗
PubMed1989

Prevalence of hypertension in bus drivers.

1. To test whether prevalence of hypertension was higher among these bus drivers than among employed individuals in general, drivers were compared to three groups: individuals from both a national and local health survey and individuals undergoing baseline health exams prior to employment as bus drivers. 2. After adjustment for age and race, hypertension rates for bus drivers were significantly greater than rates for the three comparison groups. 3. These findings support previous results from international studies of bus drivers suggesting that exposure to the occupation of driving a bus may carry increased health risk.

Adult↗
PubMed1987

Prevalence of hypertension in bus drivers.

This paper reports the results of a cross-sectional study conducted to evaluate the prevalence of hypertension in 1500 black and white male bus drivers from a large urban transit system in the US. Data for this study were compiled from the files of an occupational health clinic which conducts biennial medical examinations for drivers' license renewal. To test whether prevalence of hypertension was higher among bus drivers than among employed individuals in general, drivers were compared to three groups: individuals from both a national and local health survey and individuals undergoing baseline health examinations prior to employment as bus drivers. After adjustment for age and race, hypertension rates for bus drivers were significantly greater than rates for each of the three comparison groups. These findings support previous results from international studies of bus drivers suggesting that exposure to the occupation of driving a bus may carry increased health risk. This research has expanded into an on-going study which has the goals of clarifying the extent of hypertension in bus drivers and identifying specific behavioural and occupational factors that may be responsible for increased risk of cardiovascular disease.

Adult↗
PubMed1986

Acute effects of routine firefighting on lung function.

We undertook a study to determine the acute effects of routine firefighting on lung function and the relationship between these acute effects and nonspecific airway responsiveness. For 29 firefighters from a single fire station, we calculated the concentration of methacholine aerosol that caused a 100% increase in specific airway resistance (Pc100). Over an 8-week period we than measured FEV1 and FVC in each firefighter before and after each 24-hr workshift and after every fire. From 199 individual workshifts without fires, we calculated the mean +/- 2 SD across-workshift change in FEV1 and FVC for each firefighter. Eighteen of 76 measurements obtained within 2 hr after a fire (24%) showed a greater than 2 SD fall in FEV1 and/or FVC compared to two of 199 obtained after routine workshifts without fires (1%; p less than .001). On 13 of 18 occasions when spirometry decreased significantly, we obtained repeat spirometry (postshift) 3-18.5 hr after fires, and on four of these occasions FEV1 and/or FVC were still more than 2 SD below baseline. Decrements in spirometry occurred as often in firefighters with high Pc100s as in those with low Pc100s. In two firefighters in whom FEV1 and FVC fell by more than 10% after fires, we repeated measurements of methacholine sensitivity, and it was increased over the prestudy baseline. These findings suggest that routine firefighting is associated with a high incidence of acute decrements in lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Sister-chromatid exchanges in lymphocytes of anatomy students exposed to formaldehyde-embalming solution.

Sister-chromatid exchanges measured in the peripheral lymphocytes of 8 non-smoking persons after exposure to formaldehyde-embalming solution during a 10-week anatomy class showed a small (P = 0.02) average increase when compared with samples obtained from the same individuals immediately before exposure began. Breathing-zone air samples collected during dissection procedures showed a mean concentration of 1.2 ppm (1.5 mg/m3) formaldehyde.

Adult↗
PubMed1984

Medicaid drug-event data: an emerging tool for evaluation of drug risk.

Post-marketing surveillance (PMS) of drugs requires access to multiple data resources covering the spectrum of drug exposures and drug-associated events. In the U.S., the Federal/State third party payment system for medical care to welfare recipients, Medicaid, maintains drug-event data by date of service. The FDA has explored this data for drug utilization studies, generation of signals of drug risk, and strengthening of hypotheses of drug associated problems. Thus far, studies suggest the data from Michigan and Minnesota, covering 1.5 million patients for 18 months, can be a useful, multifunctional tool for PMS studies. Examples of use to date are presented.

Adolescent↗
PubMed1982

A model poison control system.

Responding to the need for a poison information, education, data collection and research resource in California's Bay Area and North Coast counties, the San Francisco Bay Area Regional Poison Control Center has become an integral part of the region's emergency medical services. In the first 33 months after it opened, more than 54,000 calls for assistance were received, nearly a third from medical professionals. Through the cooperation and collaboration of public, private and university resources and interests, a cost-effective, comprehensive and accessible system has evolved for public and professional use. Through our experience a system has developed that can serve as a model for poison information services throughout the western states. Emerging public concern for toxicology issues will continue to refine this model.

Humans↗
PubMed1980

Gene transfer in intact animals.

Resistance to methotrexate was induced in bone marrow cells of mice by transformation in vitro with DNA from a drug-resistant cell line. Transformed cells were injected in vivo and haematopoietic cells expressing resistance were selected by drug treatment of recipients. Transformed cells had elevated levels of dihydrofolate reductase and demonstrated a proliferative advantage over untransformed cells, indicating successful gene transfer.

Animals↗