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Biomedical subjects

D Kalman

Publications and source records attributed to D Kalman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Biological monitoring of organophosphorus pesticide exposure among children of agricultural workers in central Washington State.

Children up to 6 years of age who lived with pesticide applicators were monitored for increased risk of pesticide exposure: 48 pesticide applicator and 14 reference families were recruited from an agricultural region of Washington State in June 1995. A total of 160 spot urine samples were collected from 88 children, including repeated measures 3-7 days apart. Samples were assayed by gas chromatography flame photometric detector for dimethylphosphate metabolites. Dimethylthiophosphate (DMTP) was the dominant metabolite. DMTP levels were significantly higher in applicator children than in reference children (p = 0.015), with median concentrations of 0.021 and 0.005 microg/ml, respectively; maximum concentrations were 0.44 and 0.10 microg/ml, respectively. Percentages of detectable samples were 47% for applicator children and 27% for reference children. A marginally significant trend of increasing concentration was observed with decreasing age among applicator children (p = 0.060), and younger children within these families had significantly higher concentrations when compared to their older siblings (p = 0.040). Applicator children living less than 200 feet from an orchard were associated with higher frequency of detectable DMTP levels than nonproximal applicator children (p =0.036). These results indicate that applicator children experienced higher organophosphorus pesticide exposures than did reference children in the same community and that proximity to spraying is an important contributor to such exposures. Trends related to age suggest that child activity is an important variable for exposure. It is unlikely that any of the observed exposures posed a hazard of acute intoxication. This study points to the need for a more detailed understanding of pesticide exposure pathways for children of agricultural workers.

Agriculture↗
PubMed1996

Use of the fluorescent micronucleus assay to detect the genotoxic effects of radiation and arsenic exposure in exfoliated human epithelial cells.

The exfoliated cell micronucleus (MN) assay using fluorescent in situ hybridization (FISH) with a centromeric probe is a rapid method for determining the mechanism of MN formation in epithelial tissues exposed to carcinogenic agents. Here, we describe the use of this assay to detect the presence or absence of centromeric DNA in MN induced in vivo by radiation therapy and chronic arsenic (As) ingestion. We examined the buccal cells of an individual receiving 6,500 rads of photon radiation to the head and neck. Exfoliated cells were collected before, during, and after treatment. After radiation exposure a 16.6-fold increase in buccal cell MN frequency was seen. All induced MN were centromere negative (MN-) resulting from chromosome breakage. This finding is consistent with the clastogenic action of radiation and confirmed the reliability of the method. Three weeks post-therapy, MN frequencies returned to baseline. We also applied the assay to exfoliated bladder cells of 18 people chronically exposed to high levels of inorganic arsenic (In-As) in drinking water (average level, 1,312 micrograms As/L) and 18 matched controls (average level, 16 micrograms As/L). The combined increase in MN frequency was 1.8-fold (P = 0.001, Fisher's exact test). Frequencies of micronuclei containing acentric fragments (MN-) and those containing whole chromosomes (MN+) both increased (1.65-fold, P = 0.07, and 1.37-fold, P = 0.15, respectively), suggesting that arsenic may have both clastogenic and weak aneuploidogenic properties in vivo. After stratification on sex, the effect was stronger in male than in female bladder cells. In males the MN- frequency increased 2.06-fold (P = 0.07) while the frequency of MN+ increased 1.86-fold (P = 0.08). In addition, the frequencies of MN- and MN+ were positively associated with urinary arsenic and its metabolites. However, the association was stronger for micronuclei containing acentric fragments. By using FISH with centromeric probes, the mechanism of chemically induced genotoxicity can now be determined in epithelial tissues.

Adult↗
PubMed1994

Scientists in the courtroom: basic pointers for the expert scientific witness.

The need for expert and unbiased participation in legal proceedings by physicians, industrial hygienists, toxicologists, environmental scientists, regulators, and similar professionals is hampered by lack of familiarity with the requirements of expert testimony and lack of opportunities for professional training in this activity. Drawing on material developed in a continuing education course offered by the University of Washington, we describe the role and process of being an expert witness and provide basic information regarding good professional practices pertaining to the testifying expert role.

Ethics, Professional↗
PubMed1993

Domains of E1A that bind p105Rb, p130, and p300 are required to block nerve growth factor-induced neurite growth in PC12 cells.

Nerve growth factor (NGF) causes PC12 cells to cease division and undergo sympathetic neuron-like differentiation, including neurite outgrowth. We have tested whether differentiation and division share overlapping control mechanisms in these cells. To do this, we have perturbed the activity of proteins known to participate in cell-cycle regulation by introducing the E1A oncogene or its mutant forms via microinjection into PC12 cells. The E1A protein binds to several putative cell cycle control proteins, including p105Rb (the product of the retinoblastoma susceptibility gene), as well as others of unknown function such as p130, p107, and p300. Similar to previous results, we find that wild-type E1A abrogates NGF-induced neurite extension. However, NGF does cause neurite outgrowth in the presence of E1A mutants known to have greatly reduced binding to either p105Rb and p130 or p300. Our experiments suggest that p105Rb, p130, and p300 may participate either in E1A-mediated inhibition of differentiation or in the NGF signal transduction pathway. We also report here that NGF affects phosphorylation of p105Rb, suggesting that Rb mediates at least some of NGF's effects. Our results raise the possibility that putative cell-cycle control proteins may participate not only in NGF-induced cessation of division but also in differentiation.

Adenovirus E1A Proteins↗
PubMed1992

The contributions to solvent uptake by skin and inhalation exposure.

Solvent exposures were assessed among 97 auto body repair workers in order to determine whether skin contact represented a significant route of exposure. Each subject's cumulative skin exposure was ranked categorically based on simple observation: 49 none, 33 incidental or low, and 15 moderate or high. The median time-weighted average air exposure to solvents was 8.4% of the American Conference of Governmental Industrial Hygienists (ACGIH) combined solvent threshold limit value (TLV) with a range of 0-62% TLV, including toluene (median 4 ppm) and xylenes (median 0.9 ppm). Urine methyl hippuric acids (MHAs, metabolites of xylenes) were low compared to the ACGIH biological exposure index (BEI) with a median of 2% and a range of 0-12% BEI but were strongly correlated with both the level of airborne xylenes and skin exposure when considered simultaneously by using analysis of covariance (R = 0.91, p less than 0.0001). MHA excretion attributable to skin exposure for 15 min or more generally was comparable to or greater than that from associated air exposure over the full work shift. This study had limited ability to assess quantitatively the contributions of toluene exposures, but there was evidence that skin exposures also contributed significantly to toluene absorption. Air sampling will substantially underestimate a worker's total solvent dose in the setting of moderate or high skin exposure. Simple observation was effective in identifying workers in this sample who appeared to have sufficient skin exposure to produce a measurable increase in solvent uptake.

Adult↗
PubMed1992

Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoperazone in serum and blister fluid.

Cefepime is a new broad-spectrum cephalosporin with excellent gram-positive and gram-negative activity including activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae. The pharmacokinetic disposition of cefepime is similar to that of ceftazidime. We compared the pharmacokinetic characteristics and the extent and duration of bactericidal activity in serum and suction-induced blister fluid after single 2-g intravenous doses of cefepime, ceftazidime, and cefoperazone given to healthy subjects. One clinical isolate each of E. cloacae, P. aeruginosa, and S. aureus was used to assess bactericidal activity. Results of the pharmacokinetic analysis were similar to previously reported data for these drugs. The high serum protein binding of cefoperazone (approximately 90%) contributed to poor blister fluid penetration. The other drugs penetrated well into this fluid compartment. Cefepime showed significantly greater bactericidal activity in serum and blister fluid against E. cloacae than the other study drugs, ceftazidime was significantly better in serum and blister fluid against P. aeruginosa, and cefoperazone was significantly better against S. aureus only in serum. None of the study drugs had significant bactericidal activity in blister fluid against S. aureus. Cefepime is a promising antimicrobial agent for the treatment of infections due to E. cloacae.

Adult↗
PubMed1990

Nerve growth factor acts through cAMP-dependent protein kinase to increase the number of sodium channels in PC12 cells.

cAMP-dependent protein kinase (PKA) and phospholipid-dependent protein kinase (PKC) play a role in nerve growth factor (NGF)-mediated differentiation. In PC12 cells, NGF causes neurite outgrowth and increases the number of voltage-gated Na+ channels. Neurite outgrowth involves in part activation of PKC. How NGF regulates Na+ channel number is unknown. Using patch-clamp techniques, we find that agents activating PKC, including phorbol esters and a ras oncogene product (p21) that induces neurites, caused little increase in channel number. In contrast, agents increasing intracellular cAMP were as effective as NGF. A specific protein inhibitor of the PKA catalytic subunit blocked increases by NGF or cAMP. Thus, NGF increases Na+ channel number in PC12 cells in part by activating PKA but apparently not PKC.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Physical, morphological, and chemical studies of dusts derived from the machining of composite-epoxy materials.

This work (in three parts) inquires into whether respirable dusts derived from the machining of six composite-epoxy materials (e.g., aircraft industry) may pose a health risk to the operators. Dust samples representative of a variety of composites and structural components were aerodynamically sized and fractionated. Bulk and fractionated samples were examined by light and electron microscopy and analyzed chemically by thermogravimetry (TGA), gas chromatography (GC) and mass spectrometry (MS). Relative fractions of respirable to total mass of bulk samples were less than 3%; aerodynamic diameters of fractionated particles ranged from 0.8 to 2.0 microns. By microscopy, bulk particles ranged from 7 to 11 microns in diameter, with mean aspect ratios from 4 to 8:1. Mean diameter of fractionated particles was 2.7 microns. By TGA, weight losses were negligible below 250 degrees C and variable but elevated at temperatures up to 860 degrees C. In assays of vapors released at 250 degrees C, GC/MS indicated a variety of compounds in different amounts for each sample. We conclude that under the present machining protocols, dusts at the tool face contained few particles of respirable size with no evidence of splitting of fibers longitudinally and were of a low volatilizable chemical content. Overall, composites were judged to be well cured and thermally stable.

Chemical Phenomena↗
PubMed1988

Calcium-dependent inactivation of the dihydropyridine-sensitive calcium channels in GH3 cells.

The inactivation of calcium channels in mammalian pituitary tumor cells (GH3) was studied with patch electrodes under voltage clamp in cell-free membrane patches and in dialyzed cells. The calcium current elicited by depolarization from a holding potential of -40 mV passed predominantly through one class of channels previously shown to be modulated by dihydropyridines and cAMP-dependent phosphorylation (Armstrong and Eckert, 1987). When exogenous calcium buffers were omitted from the pipette solution, the macroscopic calcium current through those channels inactivated with a half time of approximately 10 ms to a steady state level 40-75% smaller than the peak. Inactivation was also measured as the reduction in peak current during a test pulse that closely followed a prepulse. Inactivation was largely reduced or eliminated by (a) buffering free calcium in the pipette solution to less than 10(-8) M; (b) replacing extracellular calcium with barium; (c) increasing the prepulse voltage from +10 to +60 mV; or (d) increasing the intracellular concentration of cAMP, either 'directly' with dibutyryl-cAMP or indirectly by activating adenylate cyclase with forskolin or vasoactive intestinal peptide. Thus, inactivation of the dihydropyridine-sensitive calcium channels in GH3 cells only occurs when membrane depolarization leads to calcium ion entry and intracellular accumulation.

Animals↗
PubMed1987

The role of cyclic AMP-dependent phosphorylation in the maintenance and modulation of voltage-activated calcium channels.

The predominant class of voltage-activated Ca channels in molluscan neurons (Helix) and a mammalian cell line (GH3) do not respond to membrane depolarization under conditions that prevent cAMP-dependent phosphorylation when the cytoplasm is replaced with standard physiological saline solutions. Under normal conditions, inactivation of these channels results from Ca ion entry and accumulation inside the cell. In dialyzed neurons, inactivation is enhanced in the presence of an exogenous Ca-dependent phosphatase, and inactivated channels appear to be susceptible to Ca-dependent proteolysis. Rephosphorylation of the channels by a cAMP-dependent kinase removes inactivation and protects the channels from proteolysis. Thus, phosphorylation/dephosphorylation reactions appear to be an important means of modulating Ca channel activity and may underlie both Ca-dependent inactivation and the metabolic maintenance of the channels.

Animals↗
PubMed1986

Enzymatic regulation of calcium current in dialyzed and intact molluscan neurons.

Isolated neurons of Helix aspersa were dialyzed and voltage clamped under conditions that isolate the Ca current. The rapid time-dependent run-down, or washout, of Ca current could be slowed by addition of 1 mM EGTA to the dialysis solution. A more effective means of slowing washout was the use of agents that promote protein phosphorylation, such as cAMP, Mg-ATP and the catalytic subunit (CS) of cAMP-dependent protein kinase, along with leupeptin, a tripeptide inhibitor of proteases. In the presence of these agents, no internal EGTA was required to prevent Ca current washout. Thus, during dialysis with 100 microM leupeptin, 7 mM Mg-ATP and 20 micrograms/ml CS, the Ca current remained stable for up to several hours. The rate of Ca-dependent inactivation of the current that occurs during a depolarizing step showed only a small decline during prolonged dialysis. Under these conditions, introduction of 10 microM calmodulin plus 40 micrograms/ml calcineurin, a Ca-calmodulin-dependent phosphatase, caused a significant increase in the rate of Ca current inactivation during a depolarizing step. This increase in rate of inactivation, as well as the original inactivation, was eliminated by introduction of EGTA or replacement of external Ca with Ba, results that are consistent with the ion dependency for activation of calcineurin. When internal ATP was replaced with ATP-gamma-S, a hydrolysis-resistant analogue, the rate of Ca current inactivation slowed, providing further evidence that inactivation involves a dephosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1984

Biological availability of lead in a paint aerosol. 1. Physical and chemical characterization of a lead paint aerosol.

This study was conducted to determine the physical and chemical characteristics of an aerosol of lead-based paint, generated in an industrial spray operation, that might influence the biological availability of lead present in inhaled aerosols. Paint aerosols were collected, and mass-size distribution was determined using a portable cascade impactor under actual occupational conditions. Approx. 2% of the particulate mass collected was in the respirable range (less than 10 micron mean aerodynamic diameter), although the maximum airborne concentration of lead was found to be 2-3 mg/m3. The lead concentration in a dried aerosol was very resistant to chemical digestion. Analysis by X-ray diffraction, atomic absorption spectroscopy and inductively coupled plasma emission spectroscopy showed approx. 11% lead by dry weight, although the wet weight concentration of lead reported by the manufacturer was 12.8%.

Aerosols↗