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Biomedical subjects

D Levy

Publications and source records attributed to D Levy.

At least 325 records · Page 18Linked to original sources

Acetylcholinesterase prophylaxis against organophosphate poisoning. Quantitative correlation between protection and blood-enzyme level in mice.

Fetal bovine serum acetylcholinesterase (FBS-AChE, EC 3.1.1.7) was titrated, both in vitro and in vivo, with a highly toxic anti-ChE organophosphate, 7-(methylethoxyphosphinyloxy)-1-methyl-quinolinium iodie (MEPQ). Approximately 1:1 stoichiometry was obtained for the sequestration of MEPQ by FBS-AChE in mice. A quantitative, linear correlation was demonstrated between blood-AChE levels and the protection afforded by exogenously administered AChE in mice when challenged with anti-ChE MEPQ. The results presented in this report demonstrate that such prophylactic measures are indeed sufficient to protect animals against poisoning by as high as an 8 x LD50 dose of organophosphate without the administration of any supportive drug. Despite the relatively large toxic dose, most of the mice that survived the challenge did not show any classical clinical signs of severe anti-ChE poisoning. MEPQ may be considered a suitable model compound for studying the quantitative aspects of the scavenger prophylactic approach described here.

Acetylcholinesterase↗

Left ventricular mass and incidence of coronary heart disease in an elderly cohort. The Framingham Heart Study.

OBJECTIVE: To examine the association of echocardiographically determined left ventricular mass with incidence of coronary heart disease in an elderly cohort. DESIGN: Cohort study with a follow-up period of 4 years. SETTING: Population-based. SUBJECTS: Elderly original volunteer subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease. This group included 406 men (mean age, 68 years: range, 60 to 90) and 735 women (mean age, 69 years: range, 59 to 90). MEASUREMENTS AND MAIN RESULTS: During 4 years of follow-up, coronary heart disease events occurred in 37 men and 33 women. Baseline echocardiographically determined left ventricular mass was associated with incidence of coronary disease in both sexes (P less than 0.01). After adjusting for age, systolic blood pressure, smoking, and the ratio of total/high density lipoprotein cholesterol, the relative risk for a coronary event, per 50 g/m increment in left ventricular mass/height, was 1.67 in men (95% CI, 1.24 to 2.23) and 1.60 in women (95% CI, 1.10 to 2.32). CONCLUSIONS: Echocardiographic assessment of left ventricular mass offers prognostic information beyond that provided by traditional risk factors, which can improve our ability to identify individuals at high risk for coronary heart disease. These findings may have widespread implications regarding the applications of echocardiography in clinical practice.

Age Factors↗

Changes in nerves and neuropeptides in skin from 100 leprosy patients investigated by immunocytochemistry.

The cutaneous innervation is now known to contain neuropeptides including substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory nerves, and vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), principally in autonomic nerves. Skin biopsies from 100 leprosy patients and equivalent areas from 50 non-leprosy controls were fixed in p-benzoquinone solution for immunofluorescence staining and in Bouin's fluid for classification of leprosy type. Antisera to the neural markers, neurofilaments, and protein gene product 9.5 (PGP 9.5), and to neuropeptides were used. Cutaneous nerves and nerve endings immunoreactive for neuropeptides, neurofilaments, and PGP 9.5 were seen in all non-leprous control cases. In leprosy, PGP 9.5- and neurofilament-immunoreactive nerve fibres were seen in all 14 cases of the indeterminate (early) type and in the majority (33/43) of lepromatous cases, but in a smaller proportion (15/43) of tuberculoid cases. Neuropeptide immunoreactivity was seen in only 2/14 of the indeterminate leprosy specimens and was completely absent in other types. This early disappearance may be of diagnostic significance. Thus, cutaneous sensory and autonomic dysfunctions in leprosy are well reflected by changes in nerve fibres and neuropeptides.

Calcitonin↗

Nonparametric comparison of entire ROC curves for computerized ECG left ventricular hypertrophy algorithms using data from the Framingham Heart Study.

A computer program may be capable of several different statements for left ventricular hypertrophy (eg, possible LVH, probable LVH, consistent with LVH), but such statements resulting from discretized levels of sensitivity/specificity would represent only isolated points on a receiver-operating characteristic (ROC) curve, which is a plot of all levels of sensitivity versus specificity. Even if two algorithms use the same discrete scales, their performances may not readily be compared. The authors present a comparison methodology for ROC curves using ROC area as a nonparametric measure of the ability of the algorithm to separate the two populations; the ROC area ranges from 0.5 (no ability) to 1.0 (perfect separation) and is unbiased if the normal versus abnormal populations have no common values for the measurement. The methodology compares the performance of ECG algorithms on the same population of cases by testing for significant differences of ROC areas and incorporating correlation of the algorithms in a nonparametric way. To illustrate this methodology, they use ECG and echocardiographic data from the Framingham Heart Study.

Algorithms↗

Risk factors for long-term coronary prognosis after initial myocardial infarction: the Framingham Study.

The role of standard coronary heart disease risk factors in predicting the long-term risk of recurrent coronary events in survivors of myocardial infarction is examined. Of 697 subjects (464 males and 233 females) who experienced an initial myocardial infarction during 30 years of follow-up in the Framingham Study, 459 returned for a baseline examination and were followed for up to 32 years (mean = 9.7 years) for incident reinfarction or coronary death. The Cox proportional hazards model was used to evaluate the relation of postinfarction risk factors with reinfarction and coronary death. Age-adjusted analyses showed the risk of reinfarction to be positively associated with blood pressure and serum cholesterol. Risk of coronary death was strongly associated with blood sugar level, systolic blood pressure, serum cholesterol, heart rate, diabetes, and interim reinfarction. In multivariable analyses, systolic pressure, serum cholesterol, and diabetes were predictive of reinfarction; relative weight was inversely associated with reinfarction. Systolic pressure, serum cholesterol, and the prevalence of diabetes persisted as independent predictors of coronary death. When adjustments were made for the effects of these variables, women were at only half the risk of coronary death compared with men. Higher baseline risk factors in women compared with men may obscure an important survival advantage in women. In persons recovered from an initial myocardial infarction, standard risk factors, particularly systolic pressure, serum cholesterol, and diabetes, remain important determinants of coronary prognosis over many years and warrant attention in preventing subsequent events.

Blood Pressure↗

A comparison of two methods for measuring thermal thresholds in diabetic neuropathy.

Thermal thresholds can be measured psychophysically using either the method of limits or a forced-choice method. We have compared the two methods in 367 diabetic patients, 128 with symptomatic neuropathy. The Sensortek method was chosen for the forced-choice device, the Somedic modification of the Marstock method for a method of limits. Cooling and heat pain thresholds were also measured using the Marstock method. Somedic thermal thresholds increase with age in normal subjects, but not to a clinically significant degree. In diabetics Marstock warm threshold increased by 0.8 degrees C/decade, Sensortek by 0.1 degrees C/decade. Both methods had a high coefficient of variation in normal subjects (Sensortek 29%, Marstock warm 14%, cool 42%). The prevalence of abnormal thresholds was similar for both methods (28-32%), though Marstock heat pain thresholds were less frequently abnormal (18%). Only 15-18% of patients had abnormal results in both tests. Sensortek thresholds were significantly lower on repeat testing, and all thresholds were higher in symptomatic patients. Both methods are suitable for clinical thermal testing, though the method of limits is quicker. In screening studies the choice of a suitable apparatus need not be determined by the psychophysical basis of the test.

Adolescent↗

Variable-flip-angle spin-echo MR imaging of the pelvis: more versatile T2-weighted images.

Dependence on T1 contrast can be reduced by changing the excitation flip angle. The authors compared T2-weighted spin-echo images (with 30 degrees and 90 degrees flip angles) of the male and female pelvis in 22 individuals. In six women imaged with a 1,000/80 sequence (repetition time msec/echo time msec), signal difference-to-noise ratios (SD/Ns) were higher with a 30 degree flip angle than with a 90 degree angle for urine/fat (mean, 15.2 vs -6.2; P less than .05) and endometrium/myometrium (13.8 vs 9.0, P less than .05). In eight additional examinations, a 1,000/80 sequence with a 30 degree flip angle and two signal averages had less motion artifact (1.2 vs 2.7, P less than .01) than a 2,000/80 sequence with a 90 degree angle and one signal average (4.5 minutes each); SD/Ns were similar. In a third series of experiments, contiguous sections without cross talk, obtained by interleaving two 1,000/100, 30 degrees-flip-angle acquisitions, had better contrast than contiguous sections obtained at 2,400/100 with a 90 degree flip angle (10 minutes each), with SD/Ns of urine/fat of 28.5 versus 16.1 (P less than .01) and SD/Ns of endometrium/myometrium of 15.5 versus 7.8 (P less than .05). Reducing the flip angle can improve examination time, contrast, or motion artifact suppression or eliminate cross talk in T2-weighted spin-echo MR imaging of the pelvis.

Female↗

Effect of ultrasound on transdermal drug delivery to rats and guinea pigs.

The effect of therapeutic range ultrasound (1 MHz) on skin permeation of D-mannitol, a highly polar sugar alcohol, inulin, a high molecular weight polysaccharide and physostigmine, a lipophilic anticholinesterase drug was studied in rats and guinea pigs. D-Mannitol and inulin are totally and rapidly excreted, once they have penetrated through the skin into the blood stream, permitting direct in vivo monitoring. For evaluating skin penetration of physostigmine the decrease of whole blood cholinesterase was measured. Ultrasound nearly completely eliminated the lag time usually associated with transdermal delivery of drugs. 3-5 min of ultrasound irradiation (1.5 W/cm2 continuous wave or 3 W/cm2 pulsed wave) increased the transdermal permeation of inulin and mannitol in rats by 5-20-fold within 1-2 h following ultrasound application. Ultrasound treatment also significantly increased (P less than 0.05) the inhibition of cholinesterase during the first hour after application in both physostigmine treated rats and guinea pigs: while in control guinea pigs no significant inhibition of cholinesterase could be detected during the first 2 h after application of physostigmine, the ultrasound treated group showed a 15 +/- 5% (mean +/- SEM) decrease in blood cholinesterase 1 h after ultrasound application. For physostigmine-treated rats the level of cholinesterase inhibition 1 h after ultrasound application was 53 +/- 5% in the ultrasound-treated group and 35 +/- 5% in the controls.

Administration, Cutaneous↗

Traffic safety effects of sobriety checkpoints and other local DWI programs in New Jersey.

We examined the efficacy of three Driving While Intoxicated (DWI) programs in New Jersey from 1980 through 1985, using covariance analysis of county data. Road blocks, the major component of the Strike Force program, were associated with a drop of 10-15 per cent in the single vehicle nighttime crash rate and showed a relatively stable effect over time. DWI Task Force, an education program, was associated with a 6-10 per cent total decline in the crash rate and declining impact over time. SOBER, another education program, was associated with a small effect in the first year and little or no effect thereafter.

Accidents, Traffic↗

In vivo inhibition of bovine leukemia virus (BLV) expression.

Bovine leukemia virus-infected sheep were demonstrated to possess a plasma factor that specifically suppresses in vitro virus expression in lymphocyte cultures. This blocking activity is observed even after phytohemagglutinin (PHA) stimulation and is independent of cellular proliferation. Such a factor may play a critical role in the regulation of BLV expression.

Animals↗

Further phenotypic characterization of target cells for bovine leukemia virus experimental infection in sheep.

To determine the phenotype of target cells for bovine leukemia virus (BLV) infection in sheep, we analyzed blood lymphocytes from BLV-infected clinically healthy and leukemic sheep by use of monoclonal antibodies. In clinically healthy and leukemic sheep that were BLV-infected, the blood concentration of T lymphocytes was within normal values, but the number of B lymphocytes was increased in several cases. In addition, the number of blood lymphocytes expressing the BLV antigen correlated well with that of B lymphocytes. Double immunofluorescence staining demonstrated that lymphocytes expressing BLV antigens bore B-cell but not T-cell surface markers. Moreover, neoplastic cells in the lymph nodes of leukemic sheep were stained immunohistochemically with an anti-B monoclonal antibody but not with any of anti-T monoclonal antibody tested, indicating that tumor cells are of B-lymphocyte origin. Collectively, these results show that BLV antigen-positive cells obtained from BLV-infected sheep that have no clinical signs and BLV-induced lymphosarcoma cells belong to the B-lymphocyte lineage.

Animals↗

Lactoferrin decreases monocyte-induced fibroblast production of myeloid colony-stimulating activity by suppressing monocyte release of interleukin-1.

Lactoferrin (Lf) is a negative regulator of myelopoiesis which operates by suppressing the release from mononuclear phagocytes of GM colony-stimulating factor (GM-CSF) or monokines which can then induce the release of GM-CSA from accessory cells. In this study, endotoxin-depleted, purified iron-saturated human Lf was assessed for its effect on the production of interleukin-1 by cultured monocytes and their subsequent effect on colony-stimulating factor release from cultured fibroblasts. Monocytes were grown with or without Lf and Lf that had previously been incubated with monoclonal anti-Lf. The monocyte-conditioned medium was then either assayed for the presence of interleukin-1 (IL-1) with an enzyme-linked immunosorbent assay or for its ability to stimulate fibroblasts to release growth factors for CFU-GM, BFU-E, or CFU-Mix colonies. In the presence of Lf (10(-7) or 10(-8) mol/L), GM colony-stimulating activity (GM-CSA) was suppressed by 31% to 73%, whereas stimulating activities for BFU-E and CFU-mix colony formation were suppressed by 93% to 100%. Antibody to Lf completely abrogated the suppressive effects observed with Lf, whereas antibody to IL-1 ablated the induction by monocyte-conditioned medium of CSA release by fibroblasts. Lf at 10(-7) and 10(-8) mol/L also reduced IL-1 synthesis by cultured monocytes from 60% to 77%. The inhibitory effects of Lf were only observed when Lf was added before adherence of the monocytes for culture. If Lf was added at the time of adherence or after adherence, no suppression was observed. We conclude that the inhibition of GM-CSA production/release by Lf is mediated through inhibition of the synthesis/release of IL-1 by mononuclear phagocytes. This inhibition of IL-1 prevents accessory cells from producing and/or releasing GM-CSA.

Bone Marrow Cells↗

Phase II trial of 4'-epi-doxorubicin in locally advanced or metastatic gastric cancer.

Patients with locally advanced or metastatic gastric adenocarcinoma received an i.v. bolus of 4'-epi-doxorubicin, 75/mg/m2/cycle, every 21 days. Partial responses were observed in 5 of 23 evaluable patients (21.7%). Treatment was generally well tolerated and toxicity was mild. The response rate to epirubicin appears to be very similar to that reported for doxorubicin. Larger doses of epirubicin could be safely used in future studies, and further evaluation of epirubicin in phase III trials is indicated.

Adenocarcinoma↗

Identification of the hepatocyte Na+-dependent bile acid transport protein using monoclonal antibodies.

Monoclonal antibodies have been utilized to characterize the hepatocyte Na+-dependent bile acid transport system. Sinusoidal plasma membrane proteins in the 49-54-kDa range, which are thought to be components of this transport system, based on photo-affinity labeling and reconstitution studies, have been partially purified by affinity chromatography and utilized as an immunogen for the production of a panel of monoclonal antibodies (mAb). One of these mAbs, 25A-3, recognized both a 49- and a 54-kDa protein as assessed by immunoprecipitation. In addition, it was shown to protect the bile acid transport system from inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a dose-dependent manner. DIDS covalently labeled membrane proteins of 49 and 54 kDa, and this process could be significantly inhibited when performed in the presence of mAb 25A-3. Furthermore, the DIDS-labeled membrane proteins were immunoprecipitated by 25A-3. These results establish that one of these membrane components is the bile acid carrier protein. Another mAb (25D-1) which immunoprecipitated only a 49-kDa protein was shown to block the protective effect of 25A-3 on DIDS inhibition of bile acid transport. In addition both antibodies effected each other's binding capacity to hepatocytes and reacted with the same 49-kDa protein as established by sequential immunoprecipitation. Binding studies indicated that there are approximately 3.3 X 10(6) 49-kDa transport molecules/hepatocyte. These results firmly establish that the 49-kDa protein is the Na+-dependent hepatocyte bile acid transporter.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗