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Biomedical subjects

L Morse

Publications and source records attributed to L Morse.

10 recordsLinked to original sources
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↗