Pharmacology, Toxicology and Environmental Health Commons^™

Phase Ia/Ib Trial Of Anti-Gd2 Chimeric Monoclonal Antibody 14.18 (Ch L4.18) And Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (Rhgm-Csf) In Metastatic Melanoma, James Murray, Eugenie Kleinerman, Shu-Fang Jia, Michael Rosenblum, Omar Eton, Antonio Buzaid, Sewa Legha, Merrick Ross, Lora Thompson, Mansoor Saleh

Haematology and Oncology, East Africa

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral …

Fish Tissue Contamination In Maine Lakes : Data Report, Jeanne Difranco, Linda Bacon, Barry Mower, David Courtemanch

Maine Collection

Fish Tissue Contamination in Maine Lakes : Data Report

by Jeanne DiFranco, Linda Bacon, Barry Mower and David Courtemanch

Regional Environmental Monitoring and Assessment Program (REMAP)

State of Maine Department of Environmental Protection, Bureau of Land and Water Quality, Division of Environmental Assessment, State House Station 17, Augusta, Maine 04333 (September 1995).

Contents: List of Figures and Tables / I. Introduction / II. Goals and Objectives / III. Experimental Design / IV. Methods / V. Data / VI. Quality Assurance-Quality Control / Appendices A-H

Managing Household Hazardous Waste Or Making A Choice To Do Something Without Going Broke, Maine State Planning Office

Maine Collection

Managing Household Hazardous Waste Or Making a Choice to Do Something Without Going Broke

State of Maine, State Planning Office, Augusta, Maine

Androscoggin Valley Council of Governments, Auburn, Maine

August 1995.

Contents: Acknowledgements / Abbreviations / Introduction / I. History of Household Hazardous Waste in Maine / II. How-To Guide for Towns / Appendixes / Bibliography

Persistent Oral Dyskinesias Induced By Long-Term Haloperidol Treatment Is Dissociated From Changes In Neostriatal B(Max) And Mrna Content For Dopamine D(2) Receptors, Nuoyu Huang

Electronic Theses and Dissertations

Due to the presumed associations of dopamine (DA) receptor supersensitivity phenomena in both long-term neuroleptic-treated tardive dyskinetic rats and neonatal 6-hydroxydopamine (n6-OHDA)-lesioned rats, we studied the influence of haloperidol on n6-OHDA-lesioned rats. At 3 days after birth rats received 6-OHDA-HBr (200 $\mu$g, bilateral intracerebroventricularly; desipramine pretreatment, 20 mg/kg, 1h) or vehicle. Two months later haloperidol (1.5/kg/day $\times$ 2 days/week for 4 weeks, then 1.5 mg/kg/day, every day for 10 months) was added to the drinking water. Spontaneous oral activity of intact and n6-OHDA-lesioned rats receiving haloperidol was reached and maintained at significantly higher levels after 15 weeks of haloperidol treatment. …

Indomethacin Reduces Splenic Red Pulp Macrophage Populations In Female New Zealand White Rabbits, Thane S. Thurmond

Electronic Theses and Dissertations

In an effort to elucidate the mechanism by which indomethacin (IN) attenuates the stimulatory effect of estradiol (E$\sb2$) on rabbit splenic red pulp macrophages (RPM), thirty-nine female New Zealand White rabbits were divided into 10 groups: ovariectomized (OVX), OVX/IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham OVX (SOVX), SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2, OVX/25 mg E$\sb2$/IN at 0.1 and 5.0 mg/kg bw/day; intact Control. Quantitative changes in RPM population in response to the treatments were measured using a 0 to 4 histologic grading scale. Estradiol treatment resulted in increased RPM grade when compared …

Altered Platelet Activating Factor Metabolism In Insulin Dependent Diabetes Mellitus, R A. Memon, S A. Saeed, A Jabbar, A Jafri, A H. Gilani, S Saleem, H Akbani

Department of Biological & Biomedical Sciences

Diabetes mellitus is associated with several abnormalities of platelet function. Recent studies have shown that the blood level of platelet activating factor (PAF), a potent inducer of platelet aggregation, is elevated in insulin dependent diabetes mellitus (IDDM) and remains unchanged in non-insulin dependent diabetes mellitus (NIDDM) patients. However, the mechanism of this increase in PAF levels has not been determined. In this study we have measured the activity of plasma PAF acetylhydrolase (an enzyme that regulates PAF levels) and lipoprotein levels in control subjects and diabetic patients. The data presented show that plasma PAF acetylhydrolase activity is significantly decreased in …

Pesticide Safety: A Photonovel, M. Susan Jones, The Kentucky Partnership For Farm Family Health & Safety

Nursing Faculty Publications

No abstract provided.

State Of Maine Handbook For Hazardous Waste Generators, Department Of Environmental Protection

Maine Collection

State of Maine Handbook for Hazardous Waste Generators

Department of Environmental Protection, Augusta, Maine 1995.

Contents: Introduction to Hazardous Waste / Purpose of This Handbook / Who Generates Hazardous Waste and How? / How Do I Determine If I Generate Hazardous Waste? / Am I a Small Quantity Generator (SQG), an SQG Plus, or a Generator? / Hazardous Waste Management Practices / Manifesting Hazardous Waste / In Summary / Appendix A - D

Phase Ii Trial Of Murine Monoclonal Antibody D612 Combined With Recombinant Human Monocyte Colony-Stimulating Factor (Rhm-Csf) In Patients With Metastatic Gastrointestinal Cancer, Mansoor Saleh, Michael Khazaeli, Richard Wheeler, Pat Bucy, Tiepe Liu, Michael Everson, David Mun, Jeff Schlom

Haematology and Oncology, East Africa

In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 ug/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral mono- cytosis (peak absolute monocyte count, 1444 ±394/mm3) and thrombocytopenia (nadir count, 78 ±10/nim '). Monocyte surface marker analysis revealed a …

Cd16+ Monocytes In Patients With Cancer: Spontaneous Elevation And Pharmacologic Induction By Recombinant Human Macrophage Colony- Stimulating Factor, Mansoor Saleh, Goldman Samuel, Lobuglio Albert, Beall Arthur, Sabio Hernan, Mccord Melissa, Minasian Lori, Alpaugh Katherine, Weiner Louis, Munn David

Haematology and Oncology, East Africa

The small subset of circulating monocytes that express the maturation- associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled in a clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill …

A Comparative Pharmacokinetic Study Of The Role Of Gender And Developmental Differences In Occupational And Environmental Exposure To Benzene, Elizabeth A. Brown

Theses and Dissertations

The purpose of this study is two-fold. First, it shows that physiological differences between men and women result in gender-specific exposures with respect to benzene. Second, it assesses the potential for a lactating woman's occupational and personal benzene exposure to impact a nursing infant's exposure, highlighting the possibility of subjecting an infant to the effects of industrial chemicals via breast feeding. This study employs physiologically based pharmacokinetic (PBPK) modeling to investigate the influence of physiological parameters and to evaluate the ability of inhaled benzene to transfer from mother to infant through breastmilk. The models are run through scenarios that simulate …

A Retrospective Quantitative Assessment Of Trichloroethylene Exposure Of Workers At Aircraft Maintenance Facilities At Hill Air Force Base Through The Use Of Modeling, Anthony O. Copeland

Theses and Dissertations

Monte Carlo simulation and source-receptor modeling are used to estimate the TCE exposures encountered by select workers at aircraft maintenance facilities at Hill Air Force Base between 1955 and 1979. An epidemiological study of this group, a retrospective cohort study of 14,457 workers who were employed at the base for a minimum of one year between 1952 and 1956, was headed by Dr. R. Spirtas of the National Cancer Institute to evaluate mortality associated with occupational exposure. One of the major conclusions of the study was that TCE 'probably does not pose a strong carcinogenic risk for man.' In the …

Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott

Loma Linda University Electronic Theses, Dissertations & Projects

The present studies demonstrate that in the second (2B) and fourth (4B) branches of newborn and adult sheep middle cerebral arteries, 5-HT2 serotonergic receptors mediate contractile responses to serotonin and that alpha-1 adrenergic receptors mediate contractile responses to norepinephrine. In addition, tissue sensitivity to 5-HT and NE decreases significantly with maturation, but does not vary with branch order. These age-related changes were associated with a decrease in affinity and maximum response in 2B and 4B segments of 5-HT and NE contracted arteries, respectively. Norepinephrine and 5-HT occupancy at the pD₂ rose significantly in 2B segments, but did not change …

Differential Role Of The Endothelium In Regulating Microvascular Blood Flow, Tao Tang

Electronic Theses and Dissertations

The vascular endothelial cell (EC) plays an important role in regulating vascular tone and local blood flow by sensing chemical and mechanical stimuli on the vascular wall and releasing a host of vasoactive substances upon activations of endogenous or exogenous vasoactive substances. The central hypothesis is that local control of blood now and autoregulatory behavior in the microcirculation is distinctive at different levels of the vasculature and is dependent on the cellular activities of the EC and its interaction with the local environment. The in vivo as well as the ex vivo, flow-controlled preparations of the hamster cheek pouch were …

Denervation Supersensitivity Of The Rat Vas Deferens: A Role For Protein Kinase C, Sonny T. Abraham

Electronic Theses and Dissertations

A role for protein kinase C (PKC) in the denervation-induced supersensitivity of the rat vas deferens was investigated. Chronic, surgical denervation of the rat vas deferens (up to 8 days) resulted in tissues that produced enhanced contractile responses to norepinephrine (NE) in isolated organ baths. Single challenges of NE (10 $\mu$M) produced 0.6 $\pm$ 0.1 g of maximal tension in the control vas whereas in the paired, denervated tissue 2.2 $\pm$ 0.3 g of tension was recorded (n = 6). Cumulative concentration-effect curves to NE produced in the denervated vas deferens were shifted 18-fold to the left of the control …

Characterization Of The Vasoactivity Of Tachykinins In Isolated Rat Kidney: Functional Studies And In Vitro Receptor Autoradiography, Yuejin Chen

Electronic Theses and Dissertations

Although tachykinins have potent vascular actions, their effect on renal resistance blood vessels is currently unknown. The vasoactive properties of tachykinins and related analogs were assessed in isolated perfused rat kidney. At a basal perfusion pressure (PP) of 75 $\pm$ 6 mm Hg (n = 5), bolus injections of substance P (SP) had no significant vasoactive effect. Following a sustained increase in baseline PP (134 $\pm$ 10 mm Hg) produced by phenylephrine (1 $\mu$M), SP evoked a dose-dependent increase in PP. The largest dose of SP increased PP by 60 $\pm$ 5 mm Hg. The vasoconstrictor response to SP was …

Review Of: National Research Council, Issues In Risk Assessment, Diane M. Albert

RISK: Health, Safety & Environment (1990-2002)

Review of: National Research Council, Issues in Risk Assessment (National Academy Press). Appendices, executive summary, figures, preface, references, tables. LC 92-61838; ISBN 0-309-04786-2. [374 pp. Paper $37.50 - S&H, $4 for first and $0.50 for each additional copy. 2101 Constitution Avenue, NW, Washington DC 20418.]

Review Of: M. Stuart Madden, Toxic Torts Deskbook, Laura Marron

RISK: Health, Safety & Environment (1990-2002)

M. Stuart Madden, Toxic Torts Deskbook (Lewis Publishers 1992). Acknowledgements, case index, general index, notes, preface. LC 91-48238; ISBN 0- 87371-508-X. [230 pp. Cloth $69.95 domestic, $84.00 elsewhere. 2000 Corporate Boulevard, NW, Boca Raton FL 33431.]Review of:

Validation Of A Bag Sampling Method For 1,3-Butadiene, Lori Eckenrode

Community & Environmental Health Theses & Dissertations

At this time there is no NIOSH approved means for bag sampling 1,3-butadiene. An attempt was made to use the application of cold (0°F) to inhibit the reactivity of the gas prior to analysis. The State of California Air Resources Board has an approved method for the gas chromatographic analysis of 1,3-butadiene from stationary sources. The method was utilized in the application of industrial hygiene monitoring of affected workers. The application of cold was found to be ineffective at inhibiting the highly reactive nature of 1,3-butadiene. Analyte losses were too great to classify the method as an accurate measure of …

Co-Sensitization Of Dopamine And Serotonin Receptors Occurs In The Absence Of A Change In The Dopamine D1 Receptor Complex After A Neonatal 6-Ohda Lesion, Li Gong

Electronic Theses and Dissertations

To test whether SKF 38393 could ontogenetically sensitize dopamine (DA) D$\sb1$ receptors and whether this sensitization would be associated with biochemical changes, intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (200 $\mu$g i.c.v.) were treated daily from birth with SKF 38393 (3.0 mg/kg i.p. x 28 days) or its vehicle. In DA D$\sb1$ neonatally sensitized 6-OHDA rats, enhanced locomotor responses were observed with the first SKF 38393 challenge dose (3.0 mg/kg i.p.) at 6 weeks. This response increased further with weekly SKF 38393 treatments. Enhanced stereotyped behaviors were seen in both lesioned and sensitized rats at 8 weeks. There was no change …

Regulate Pollution Or Land Use - Managing Toxic Air Contaminants In Southern California, Marc Dohan

RISK: Health, Safety & Environment (1990-2002)

A California air quality management district recently proposed to limit the location of potential receivers, in contrast with sources, of air toxics. The author argues that, although this particular proposal was later abandoned, it amounted to land use regulation. He also argues that such action usurps local control and is unwarranted.

A Risk Assessment Of The Health Liabilities From Exposure To Toxic Metals Found In The Composted Material Of Air Force Municipal Solid Waste, Timothy L. Merrymon

Theses and Dissertations

This thesis assesses the risk of the health liabilities from exposure to toxic metals found in the composted material of Air Force municipal solid waste (MSW). The goal is to determine the probability that the composted MSW could be a health hazard if it were used as a soil amendment. The research limited the assessment of the exposure risk to heavy metals found in raw MSW and its resulting compost. The thesis uses reviews of present literature to examine the food and soil ingestion exposure pathways. These pathways are assessed using the heavy metal concentrations found in MSW compost and …

Toxics Use Reduction: Pro And Con, Francine Laden, George M. Gray

RISK: Health, Safety & Environment (1990-2002)

With the Massachusetts Toxics Use Reduction Act as an example, important issues related to the goals and effectiveness of TUR are examined. The benefits as claimed by proponents are contrasted with shortcomings outlined by opponents in point-counterpoint style. Ultimately, the authors call for more balanced analysis.

Book Review, James R. Baum

RISK: Health, Safety & Environment (1990-2002)

Review of: MANAGEMENT OF HAZARDOUS AGENTS. Vol. 1: INDUSTRIAL AND REGULATORY APPROACHES. Vol. 2: SOCIAL, POLITICAL, AND POLICY ASPECTS. (Duane G. LeVine & Arthur C. Upton eds., Praeger 1992). Each volume contains: bibliography, series foreword, foreword, figures, notes, biographical references, tables, index. Vol. 1: [194 pp.] LC-92-167 ISBN 0-275-94322-4. Vol. 2: [188 pp.] ISBN 0-275-94323-2. [Cloth, each $49.95. 88 Post Road West; Westport CT 06881.]

Treat It Right : Alternative Wastewater Systems That Protect Water Quality, Brian Kent

Maine Collection

Treat It Right : Alternative Wastewater Systems That Protect Water Quality

Maine Dept. of Environmental Protection : Maine Dept. of Economic & Community Development, February 1993.

"This handbook was prepared by Maine Tomorrow, a consulting firm in Hallowell. Maine. The handbook was researched, written and designed by Brian Kent; the primary editor and research associate was Alison Truesdale, and Wendy Mahoney did the wordprocessing and desk-top printing."

Effect Of Alcohol On The Postnatal Development Of Cerebellar Cortex In Rat Guste 1-Histological And Morphometric Studies., Mansoor Saleh, M N. Saleh, M A. Desouky, Saadia Sayed, Entesar Saber

Haematology and Oncology, East Africa

The effect of ethyl alcohol (10%) on the postnatal development of cerebellar cortex was studied using histological and morphometric methods. The external granular layer was much increased in thickness in alcohol fed rat than those of the control while the molecular and granular layer were reduced. The cells of themolecular layer showed neuronal degeneration and many spaces were present in this layer esp < /strong>ecially late postnatal. The Purkinje cells failed to reach their final position up the tenth day and still arranged in more than one row. The degenerative changes appeared at five days and increased with age. The extent …

Identification And Characterization Of Possible Multiple Binding Sites For ((3)H)8-Oh-Dpat In The Hippocampus, Dawna Lea Evans

Masters Theses

No abstract provided.

The Effect Of Trimethyltin On The Cholinergic System Of The Rat Hippocampus, Richard L. Cannon

Electronic Theses and Dissertations

Trimethyltin (TMT) is a neurotoxin occurring in the environment. Exposure to (TMT) is known to destroy specific neuronal components of the hippocampus in the rat and to cause clinical symptoms in exposed humans, including mnemonic deficits, that indicate hippocampal involvement. In addition to hippocampal cell loss TMT causes significant increases in cholinergic markers such as acetylcholinesterase (AChE) stain density and choline acetyltransferase (ChAT) activity in the hippocampus of rats. However, despite these observations the effect of TMT on hippocampal cholinergic system has not been investigated in detail. The purpose of the present study was to elucidate more fully the consequences …

On The Mechanism Of Parathyroid Hormone Stimulation Of Calcium Uptake By Mouse Distal Convoluted Tubule Cells, F A. Gesek, A. Friedman

Dartmouth Scholarship

PTH stimulates transcellular Ca2+ absorption in renal distal convoluted tubules. The effect of PTH on membrane voltage, the ionic basis of the change in voltage, and the relations between voltage and calcium entry were determined on immortalized mouse distal convoluted tubule cells. PTH (10(-8) M) significantly increased 45Ca2+ uptake from basal levels of 2.81 +/- 0.16 to 3.88 +/- 0.19 nmol min-1 mg protein-1. PTH-induced 45Ca2+ uptake was abolished by the dihydropyridine antagonist, nifedipine (10(-5) M). PTH did not affect 22Na+ uptake. Intracellular calcium activity ([Ca2+]i) was measured in cells loaded with fura-2. Control [Ca2+]i averaged 112 +/- 21 nM. …

Fixed-Ratio Size As A Determinant Of The Development Of Tolerance To Morphine, Mark J. Nickel

Masters Theses

The acute and chronic effects of morphine were examined in pigeons exposed to a multiple schedule with fixed ratio 5, 25, and 125 components. Acute exposure to morphine (0.56-10.0 mg/kg) resulted in rate reductions under each component when the dose was 1 mg/kg or higher. With chronic exposure to 5.6 mg/kg, tolerance to the rate-reducing effects of morphine was evident under each fixed ratio component. The development of tolerance was determined to some extent by fixed-ratio size, a result similar to earlier findings with cocaine.