Biomedical subjects

J Moore

Publications and source records attributed to J Moore.

At least 199 records · Page 11Linked to original sources

PubMed1998

The usefulness of CD64, other monocyte-associated antigens, and CD45 gating in the subclassification of acute myeloid leukemias with monocytic differentiation.

Immunophenotyping by flow cytometry is widely used in the diagnosis and subclassification of acute myeloid leukemia (AML). CD14 is the monocyte-associated antigen most widely used to identify AML with monocytic differentiation (French-American-British classes M4 and M5); however, we observed that CD14 expression is frequently diminished or absent in such cases. To identify monocyte-associated antigens that might improve recognition of AML M4 and M5, we used 3-color flow cytometry and a panel of antibodies reported to distinguish cells of monocytic lineage in 44 cases of AML. In addition, CD45 vs logarithmic side scatter plots were analyzed in all cases. As expected, CD14 was highly specific but was only moderately sensitive for monocytic differentiation. CD64 had the best-combined sensitivity and specificity for AML M4 and M5. CD45 vs logarithmic side scatter analysis showed a higher percentage of monocytes in AML M4 and M5 compared with nonmonocytic AML. CD64 was expressed in 5 of 5 cases of acute promyelocytic leukemia (AML M3), but the intensity of staining was significantly less in AML M3 than in AML M4 and M5. Our findings show that addition of CD64 and CD45 vs logarithmic side scatter analysis to CD14 greatly improves flow cytometric detection of AML with monocytic differentiation and that CD64, also expressed in AML M3, may help distinguish AML M3 from other subtypes.

Flow Cytometry↗

PubMed1998

Lumbosacral cerebrospinal fluid volume is the primary determinant of sensory block extent and duration during spinal anesthesia.

UNLABELLED: BACKGROUND. Injection of local anesthetic into cerebrospinal fluid (CSF) produces anesthesia of unpredictable extent and duration. Although many factors have been identified that affect the extent of spinal anesthesia, correlations are relatively poor and the extent of spread remains unpredictable. This study was designed to determine whether variability in the volume of lumbosacral CSF among individuals is a contributing factor in the variability of spinal anesthesia. METHODS: Spinal anesthesia was administered to 10 healthy volunteers with 50 mg lidocaine in 7.5% dextrose. The technique was standardized to minimize variability in factors known to affect the distribution of spinal anesthesia. The extent of sensory anesthesia was assessed by pin-prick and by transcutaneous electrical stimulation. Motor blockade was assessed in the quadriceps and gastrocnemius muscles by force dynamometry. Duration of anesthesia was assessed by pinprick, transcutaneous electrical stimulation, and duration of motor blockade. Lumbosacral CSF volumes were calculated from low thoracic, lumbar, and sacral axial magnetic resonance images obtained at 8-mm increments. Volumes of CSF were correlated with measures of extent and duration of spinal anesthesia using the Kendall rank correlation test. RESULTS: Lumbosacral CSF volumes ranged from 42.7 to 81.1 ml. Volumes of CSF correlated with pin-prick assessments of peak sensory block height (P = 0.02) and duration of surgical anesthesia (as assessed by the duration of tolerance to transcutaneous electrical stimulation at the ankle (P < 0.05). CONCLUSIONS: Variability in lumbosacral CSF volume is the most important factor identified to date that contributes to the variability in the spread of spinal sensory anesthesia.

Adult↗

PubMed1998

Gas chromatography-electron ionization and chemical ionization mass spectrometric analysis of serum mexiletine concentration after derivatization with 2,2,2-trichloroethyl chloroformate: a novel derivative.

Mexiletine (Mexitil) is an antiarrhythmic agent used in the treatment of ventricular arrhythmia. The drug has a narrow therapeutic window, and monitoring its serum concentration is recommended. The authors describe a gas chromatography-mass spectrometric (GC/MS) assay of mexiletine using selected ion monitoring. Mexiletine was extracted from alkaline serum with dichloromethane followed by derivatization with 2,2,2-trichloroethyl chloroformate. The reaction was completed in 30 minutes at 70 degrees C. N-propylamphetamine was used as the internal standard. The ions monitored were m/z 58, 102, 122, 232, and 234 for derivatized mexiletine and m/z 56, 91, 131, 260, and 262 for the derivatized internal standard. The within-run precision at a serum mexiletine concentration of 1 mg/l was 1.7% (mean = 0.981, SD = 0.017 mg/l, n = 8) and the between-run precision was 3.3% (mean = 0.983, SD = 0.033 mg/l, n = 6). The assay was linear for serum mexiletine concentrations of 0.2 to 2.5 mg/l. The detection limit was 0.1 mg/l. The authors observed no carry-over problem in their assay. They observed a good correlation between mexiletine concentrations measured by a reference laboratory (Associated Regional University Pathologists, Salt Lake City, UT, U.S.A.) and by the new GC/MS assay.

Anti-Arrhythmia Agents↗

PubMed1998

Do gastrointestinal symptoms vary with the menstrual cycle?

This systematic review presents both the physiological and symptom-based studies which have explored gastrointestinal variation across the menstrual cycle. Understanding this variation may be helpful in identifying the origin of pelvic pain, particularly as the symptoms associated with causes, such as endometriosis, also vary across the cycle. One-third of otherwise asymptomatic women may experience gastrointestinal symptoms at the time of menstruation, and almost 50% of women with irritable bowel syndrome report a perimenstrual increase in symptoms.

Abdominal Pain↗

PubMed1998

An investigation into the effects of sodium citrate ingestion on high-intensity exercise performance.

This study examined the effect of sodium citrate ingestion on high-intensity cycling performance in repeated 45-sec bouts. Twelve subjects (9 male and 3 female) ingested either a sodium citrate solution (0.3 g x kg-1 body mass[BM]) or a placebo 90 min prior to exercise. Postingestion blood HCO3 concentrations were significantly higher in the citrate trial (p<.01), but there was no difference over the five bouts (p<.05) and postexercise blood lactate concentrations significantly increased over the five bouts (p<0.01), but there were no differences between trials. We conclude that sodium citrate ingestion (0.3 g x kg-1 BM) is not an effective ergogenic aid for high-intensity, intermittent exercise as simulated in this protocol.

Adult↗

PubMed1998

CD4-Induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: consequences for virus entry and neutralization.

Human immunodeficiency virus type 1 (HIV-1) entry into target cells involves sequential binding of the gp120 exterior envelope glycoprotein to CD4 and to specific chemokine receptors. Soluble CD4 (sCD4) is thought to mimic membrane-anchored CD4, and its binding alters the conformation of the HIV-1 envelope glycoproteins. Two cross-competing monoclonal antibodies, 17b and CG10, that recognize CD4-inducible gp120 epitopes and that block gp120-chemokine receptor binding were used to investigate the nature and functional significance of gp120 conformational changes initiated by CD4 binding. Envelope glycoproteins derived from both T-cell line-adapted and primary HIV-1 isolates exhibited increased binding of the 17b antibody in the presence of sCD4. CD4-induced exposure of the 17b epitope on the oligomeric envelope glycoprotein complex occurred over a wide range of temperatures and involved movement of the gp120 V1/V2 variable loops. Amino acid changes that reduced the efficiency of 17b epitope exposure following CD4 binding invariably compromised the ability of the HIV-1 envelope glycoproteins to form syncytia or to support virus entry. Comparison of the CD4 dependence and neutralization efficiencies of the 17b and CG10 antibodies suggested that the epitopes for these antibodies are minimally accessible following attachment of gp120 to cell surface CD4. These results underscore the functional importance of these CD4-induced changes in gp120 conformation and illustrate viral strategies for sequestering chemokine receptor-binding regions from the humoral immune response.

Animals↗

PubMed1998

Fumagillin analog in the treatment of Kaposi's sarcoma: a phase I AIDS Clinical Trial Group study. AIDS Clinical Trial Group No. 215 Team.

PURPOSE: Angiogenesis is a major component of Kaposi's sarcoma (KS) and a critical process in tumor growth. The present study was designed primarily to test the toxicity and pharmacokinetics (PK) of the angiogenesis inhibitor TNP-470 and secondarily to evaluate tumor response in patients with early AIDS-related KS. PATIENTS AND METHODS: Patients with AIDS-related KS were required to have cutaneous disease with > or = 5 measurable lesions and no evidence of pulmonary, symptomatic gastrointestinal, or acutely life-threatening KS. Thirty-eight patients received TNP-470 by weekly intravenous infusion over 1 hour at one of six dose levels for up to 24 weeks. RESULTS: The dose levels tested included 10, 20, 30, 40, 50 and 70 mg/m2. Median CD4 count was 24 cells/microl (range, 0 to 460). Fourteen patients (36%) had > or = 50 cutaneous lesions and 19 (49%) had oral lesions. Adverse events included neutropenia (n = 2), hemorrhage (n = 3), and urticaria (n = 1). PK studies showed wide interpatient and intrapatient variability. Elimination half-life values were short (range, 0.01 to 0.61 hours). Seven patients (18%) achieved a partial response. The median time to partial response was 4 weeks (range, 2 to 25), and the median duration of response was 11 weeks (range, 3 to 26+). CONCLUSION: TNP-470, administered as a weekly, 1-hour infusion to patients with early AIDS-KS is well-tolerated at doses up to and including the highest dose tested. Tumor responses were observed in a substantial number of cases and occurred at various dose levels. TNP-470 should be evaluated further in patients with AIDS-KS as a single agent and in combination with other biologic response modifiers in early disease or after initial response to cytotoxic chemotherapy.

AIDS-Related Opportunistic Infections↗

PubMed1998

Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS.

Transforming growth factor (TGF)-beta2 is a pleiotropic cytokine associated with remissions in multiple sclerosis (MS) and amelioration of allergic encephalomyelitis. We assessed the safety of TGF-beta2 in an open-label trial of 11 patients with secondary progressive (SP) MS. Five patients had a reversible decline in the glomerular filtration rate. There was no change in expanded disability status scale or MRI lesions during treatment. Systemic TGF-beta2 may be associated with reversible nephrotoxicity, and further investigation of its therapeutic potential in MS should be performed with caution.

Adult↗

PubMed1998

A genetic deficiency that spans the flightin gene of Drosophila melanogaster affects the ultrastructure and function of the flight muscles.

We have developed a reverse-genetic approach to study the function of flightin, a unique protein of the flight muscle myofibril of Drosophila melanogaster. We describe the generation and characterization of Df(3L)fln1, a lethal genetic deficiency in the 76BE region of the third chromosome which deletes several genes, including the gene for flightin. We show that heterozygous flies harboring the Df(3L)fln1 mutation exhibit both impaired flight and ultrastructural defects in their flight muscle myofibrils. We found that the mutation does not interfere with assembly of the myofibril but leads to disorganization of peripheral myofilaments in adult myofibrils. Most myofibrils, nevertheless, retain an intact core that represents approximately 80 % of the normal lattice diameter. Mechanical analysis of single skinned flight muscle fibers demonstrates that the mutation has no significant effect on net power output but increases the frequency at which maximum power is delivered to the wings, potentially reducing the overall performance of the flight system. The results suggest that flightin is an indispensable part of the flight muscle contractile mechanism.

Animals↗

PubMed1998

13th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies and conceptual issues.

Substantial world-wide resources are being committed to develop improved toxicological testing methods that will contribute to better protection of human health and the environment. The development of new methods is intrinsically driven by new knowledge emanating from fundamental research in toxicology, carcinogenesis, molecular biology, biochemistry, computer sciences, and a host of other disciplines. Critical evaluations and strong scientific consensus are essential to facilitate adoption of alternative methods for use in the safety assessment of drugs, chemicals, and other environmental factors. Recommendations to hasten the development of new alternative methods included increasing emphasis on the development of mechanism-based methods, increasing fundamental toxicological research, increasing training on the use of alternative methods, integrating accepted alternative methods into toxicity assessment, internationally harmonizating chemical toxicity classification schemes, and increasing international cooperation to develop, validate, and gain acceptance of alternative methods.

Animal Testing Alternatives↗

PubMed1998

Choosing the right ladder: creating a new model for healthcare.

Healthcare in America needs to be fundamentally restructured if we hope to successfully overcome issues relating to cost and health outcomes. This will require a basic change in mindsets. We can no longer think of health as the mere absence of disease, nor can we afford to pigeonhole responsibility for achieving and maintaining health on a community basis. Health is not the responsibility of the local hospital, or the Public Health agency, or the inner-city clinic, or the police department, or the fire department, or the day-care center. It is the community's responsibility. We must be careful as we engage ourselves in this effort not to expect overnight success. Americans are notorious for wanting quick fixes. We cannot hope to achieve that kind of result in this effort. Although we may see some level of immediate result, this is not an endeavor where we will be able to measure huge payoffs in months or quarters. The real benefits may be a generation down the road. But if we preserve, our children will be able to look back on our efforts with gratitude that we had the courage to stay the course and do what needed to be done.

Community Health Planning↗

PubMed1998