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Biomedical subjects

E F Krieg

Publications and source records attributed to E F Krieg.

35 records · Page 2Linked to original sources

Induction of ornithine decarboxylase activity by 4,4'-methylene bis(2-chloroaniline) in the rat.

The effects of the curative extender 4,4'-methylene bis (2-chloraniline) (MOCA), an established experimental carcinogen that exhibits activity in rat liver, on hepatic ornithine decarboxylase (ODC) activity was investigated. Male Sprague-Dawley rats were injected i.p. with 75 mg/kg MOCA and killed 6, 12, 18, 24, 42 and 48 h later. Stimulation with MOCA of liver cytosolic ODC was first evident at 6 h, peaked at 12 h and returned to control levels by 42 h. The liver enzyme was refractory to stimulation by a second treatment of MOCA within the dosing intervals examined. The magnitude of stimulation of the enzyme by this aromatic amine was dependent on dose and route of administration.

Animals↗

Neurobehavioral effects from acute exposures to methyl isobutyl ketone and methyl ethyl ketone.

Subjects were tested for neurobehavioral performance in an environmental chamber to detect the presence of subclinical central nervous system effects from 4-hr exposures to methyl isobutyl ketone (MIBK) at 100 ppm, methyl ethyl ketone (MEK) at 200 ppm, MIBK at 50 ppm with MEK at 100 ppm, or a placebo (i.e., a 5-min presentation of 25 ppm MEK-MIBK at each exposure period outset). Subjects were 68 males and 75 females recruited from local universities; ages ranged from 18 to 32 years. Ethanol by ingestion (95%-0.84 ml/kg) was used as a positive control. Five psychomotor tests (choice reaction time [CRT], simple reaction time [SRT], visual vigilance, dual task [auditory tone discrimination and tracking], memory scanning), one sensorimotor test (postural sway), and a test of mood (profile of mood states) were used to measure neurobehavioral effects. Additionally, chemical measurements (blood and breath) and reports of sensory and irritant effects were measured. The chemical exposures produced statistically significant performance effects on only 4 of 32 measures (% correct responses-visual vigilance, movement time-CRT, SRT, % incorrect responses-dual task). These effects, however, were not substantial and could not be attributed directly to the chemical exposures. Alcohol ingestion, however, produced significant decrements on every performance test except memory scanning and mood. An interaction occurred between gender and alcohol ingestion, such that more statistically significant performance decrements were found for females than for males. Significant odor sensations and irritant effects were reported by the subjects during the chemical exposures. The MEK results agree with earlier MEK experiments at comparable exposure conditions, and the MIBK results are consistent with a recent Swedish study that used MIBK exposures and showed no significant behavioral performance decrements from single MIBK exposures at 50 ppm with 50 W exercise. Additionally, the MIBK-MEK combination exposure showed no evidence of any interaction effects on either the behavioral or chemical measurements. The principal effects resulting from exposures to MEK and MIBK at the durations and concentrations used in the study are limited to sensory and irritant effects.

Adolescent↗

Methods of monitoring menstrual function in field studies: efficacy of methods.

Efficacy of methods for monitoring female reproductive potential under field study conditions was evaluated. Women (n = 10) were recruited to participate for two menstrual cycles on the bases, in part, of not seeking fertility assistance, working full-time but not in the medical field, and having less than one year of college education. Luteinizing hormone (LH), estrone-3-glucuronide, and pregnanediol-3-glucuronide were measured in daily morning urine and normalized to creatinine concentrations. These urinary measures were parallel to serum LH, estradiol, and progesterone profiles. Based on these urinary measures, 6 of 19 cycles were judged to be atypical. Transvaginal ultrasonography provided insights into ovarian activity during the atypical cycles. Of 13 LH surges detected by radioimmunoassay, 7 were not detected by a semiquantitative dipstick (OvuSTICK), perhaps due to that method's sensitivity to loss of LH immunoactivity caused by sample freezing. While intervals from salivary and vaginal mucous electrical resistance signals to the LH surge during typical cycles were similar to those reported previously, they were not predictive of ovulatory status during atypical cycles. Fifty-three percent of the cycles were misclassified on the basis of the basal body temperature rise. Cervical mucous color, amount, and consistency were not predictive of ovulation under these study conditions. The results from these 19 menstrual cycles provide information about the efficacy of various methods for characterizing menstrual function under field study conditions. In this regard, urinary endocrine measures are the most informative or practical.

Adult↗

Methods of monitoring menstrual function in field studies: attitudes of working women.

This study was designed to determine the attitudes and compliance of working women toward methods being evaluated for use in the assessment of the effects of toxicants on reproductive potential. Women such as the highly motivated fertility patients and nurses, who are typically familiar with the methods and procedures of fertility assessment and the value of medical research, have been used to validate such methods in a clinical setting. However, the attitudes of a general working female population toward these methods are unknown. Nine participants were selected on the bases, in part, of not seeking fertility assistance, working full-time but not in the medical field, and having less than one year of college education. Attitudes were also evaluated for 193 non-participating women to whom the procedures had been verbally described. Participants measured basal body temperature and salivary and vaginal mucous electrical resistance, evaluated cervical mucus manually (CME), and collected the first morning urine for two menstrual cycles. Blood, saliva, and transvaginal ultrasonograms (US) were obtained at a fertility clinic 6 to 9 days per cycle. Participants brought urine to the laboratory every 3 days. All participants performed all methods. Participants were paid $400; nonparticipants were not compensated. Only 3% of the respondents objected to the proposed methods: principally to CME, US, and giving blood samples. No respondent perceived the study as unimportant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Microbreak length, performance, and stress in a data entry task.

The effects of brief rest pauses on performance and well-being were evaluated for a highly repetitive, data entry task. Experienced data entry operators (N = 20) performed the task in a two-day experiment in a simulated office environment. Each day was divided into six, 40-min work periods. Subjects took a brief rest pause at the workstation (microbreak) in the middle of each work period. Subjects were instructed to terminate this microbreak when ready to resume work. Keystroke rate, error rate, correction rate, heart rate and heart rate variability were scored for each half of the work period. In addition, mood states before and during the work period were assessed. Microbreaks were found to average 27.4 s in duration. High ratings of fatigue and boredom during the work period were associated with longer microbreaks, suggesting that the break period was self-adjusted relative to mood state. In addition, correction rate and heart rate were lower following long microbreaks, implying that the degree of recovery was linked to the length of the microbreak. Comparison of keystroke output and correction rate before and after the microbreak, however, revealed that performance worsened after the microbreak, suggesting that subjects terminated microbreaks before complete recovery could occur.

Adolescent↗

A regression model for carpal tunnel syndrome.

The purpose of this study was to determine whether a logistic regression model for the diagnosis of carpal tunnel syndrome (CTS) could be developed. Forty-eight variables were initially identified, for the 28 CTS and 34 non-CTS subjects, including 28 measures of nerve function, 6 anatomical measurements, 8 variables relating to disease symptoms, and 6 variables relating to physical attributes. An a priori clustering procedure was used to establish groups for the principal components analyses. The first principal component of each cluster was then used in a backward, stepwise logistic regression analysis. The best combination of candidate variables, as identified by the regression equation, was Raynaud's symptoms and median nerve motor function. The results of this study indicate that a model for CTS can be generated from a set of variables and that a linear combination of variables representing nerve function is closely associated with conduction decrements resulting from CTS.

Carpal Tunnel Syndrome↗

Characterization of binding sites for N-Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) in rat brain.

Binding sites for N-Tyr-Pro-Leu-Gly-NH2 (Tyr-MIF-1), a novel peptide structurally related but immunoreactively different from Pro-Leu-Gly-NH2 (MIF-1), were investigated. The presence of Tyr-MIF-1-like material in brain tissue has previously been demonstrated by RIA and its levels were shown to vary with the diurnal cycle and after pinealectomy. We now demonstrate a high affinity binding site in rat brain that is saturable and specific for Tyr-MIF-1. Crude P2 synaptosomal fractions from rat brains were incubated with 125I-Tyr-MIF-1 in the presence or absence of 10 microM unlabeled Tyr-MIF-1 (nonspecific binding). Binding reached equilibrium at 30-40 min at 23 degrees C and at about 4 hr on ice, after which it was relatively stable for at least 18 hr. None of the other peptides (including MIF-1) or amino acid residues tested were found to effectively compete for 125I-Tyr-MIF-1 binding. Binding was linear with protein from 280 micrograms to at least 1.1 mg protein per tube. Scatchard analysis of the striatum-thalamus revealed the presence of binding sites with an apparent Kp of 91 nM and maximum number of sites in the range of 45 fmol/mg tissue. Analysis of several brain areas revealed a differential distribution of the binding sites with relatively high concentrations in cortex, striatum, and amygdala and low concentrations in pons-medulla. Together with the previously published RIA results, the demonstration of a receptor for Tyr-Pro-Leu-Gly-NH2 supports the concept of the presence of this novel peptide and its receptor in the brain.

Amygdala↗

Stability of urinary female reproductive hormones stored under various conditions.

Urinary reproductive hormones afford specific and sensitive evaluation of female reproductive potential in epidemiologic and clinical settings. The goal of this study was to characterize the stability of urinary luteinizing hormone, follicle stimulating hormone, estrone 3-glucuronide, pregnanediol 3-glucuronide, and creatinine during storage as functions of time, temperature, and additives. After 2 weeks with no additives, activity of the four analytes, relative to initial concentrations, ranged from 91.9 to 102.8% at 4 degrees C, 35.1 to 89.6% at 25 degrees C, and 7.5 to 66.9% at 37 degrees C. Antimicrobial additives did not consistently improve stability. Analyte activity for samples stored with no additives for 24 weeks at -80 degrees C ranged from 69.0 to 101.2%. Glycerol and bovine serum albumin improved analyte stability; activity ranged from 91.1 to 106.3%. Other additives were ineffective. These results reveal conditions for storing reproductive hormone analytes in urine during epidemiologic field studies.

Adult↗

Behavioral teratology investigation of 1-propanol administered by inhalation to rats.

Due to their structural similarity to ethanol, a human teratogen, and their widespread use in industry, a series of industrial alcohols are being investigated for developmental toxicity. This paper presents the results of exposures to 7000 ppm 1-propanol, which is minimally toxic to maternal animals and produces a low incidence of teratogenicity, and to 3500 ppm 1-propanol, which is not toxic to maternal rats and produces no teratogenicity. Propanol vapors or filtered air was administered for 7 hr/day to 15 pregnant Sprague-Dawley rats throughout gestation or to 18 male rats daily for 6 weeks. Tests of offspring were: a) ascent on a wire mesh screen b) rotorod, c) open field and optically monitored activity, d) running wheel, e) avoidance conditioning, and f) progressive fixed ratio schedule of reinforcement. Brains from 10 rats per group were dissected into cerebrum, cerebellum, brainstem, and midbrain, and were assayed for protein, acetylcholine, dopamine, norepinephrine, serotonin, beta-endorphin, Met-enkephalin, and substance P. Overall, the results indicate that exposure to high concentrations of 1-propanol can affect fertility in exposed males (only 2 of 17 produced litters), but there were no consistent effects seen in the behavioral or neurochemical tests measured. This lack of effects is surprising based on predictions from the structural similarity of 1-propanol to ethanol, and on long-standing observations that toxicity (to adult animals) increases with carbon chain length among the aliphatic alcohols.

1-Propanol↗

Behavioral teratology investigation of 1-butanol in rats.

Two concentrations of 1-butanol (3000 and 6000 ppm) were administered by inhalation to separate groups of 15 pregnant Sprague-Dawley rats for 7 hr per day throughout gestation; 18 male rats were similarly exposed for 7 hr per day for 6 weeks, and mated to unexposed females. Litters were culled to 4 female and 4 male pups and fostered to untreated controls. From days 10-90, offspring were tested as follows: a) ascent on a wire mesh screen, b) rotorod, c) open field and photoelectrically-monitored activity, d) running wheel, e) avoidance conditioning, and f) operant conditioning. Additionally, brains from 10 offspring at 21 days of age were dissected into cerebrum, cerebellum, brainstem, and midbrain. Each sample was assayed for protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, serotonin, met-enkephalin, beta-endorphin, and substance P. Overall, there were few behavioral or neurochemical alterations detected in the offspring following maternal or paternal exposure to either 3000 or 6000 ppm 1-butanol. This scarcity of effects is important to risk assessment extrapolations drawn from ethanol. Based on the structural similarity of 1-butanol to ethanol and long-standing observations that toxicity to adult animals generally increases with chain length among the alcohols, significant behavioral and neurochemical deviations were predicted. The scarcity of effects from butanol needs to be accounted for in hypotheses relating toxicity to alcohol chain length and in risk assessment extrapolations from findings with ethanol.

Animals↗

A mathematical model of performance on a simple reaction time test.

A nonlinear function with components for learning and fatigue was used to model individual performance on a simple reaction time test. The relationships between the parameters of the model and the mean and variance of the reaction times are discussed. The function is used to analyze data from a field study of agricultural workers exposed to organophosphate pesticides. Exposure had a significant effect on the relationships between education level and initial performance, age and fatigue rate, and age and performance variability. Parameter estimates from the model were able to distinguish between effects that the mean and standard deviation of the reaction times were unable to distinguish.

Adolescent↗

Evaluation of acute sensory--motor effects and test sensitivity using termiticide workers exposed to chlorpyrifos.

Sensory and motor testing was performed on a group of termiticide workers primarily using chlorpyrifos-containing products to evaluate both the acute effects from current exposure and sensitivity of the measures to detect effects. The study group comprised 106 applicators and 52 nonexposed participants. Current exposure was measured by urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCP) collected the morning of testing. The mean TCP value for the 106 applicators was 200 microg/g creatinine. Participants received 4--5 h of testing and were evaluated using a sensory--motor test battery recommended by a National Institute for Occupational Safety and Health (NIOSH)-sponsored advisory panel to be appropriate for testing effects from pesticide exposures. Measurements testing olfactory dysfunction, visual acuity, contrast sensitivity, color vision, vibrotactile sensitivity, tremor, manual dexterity, eye--hand coordination, and postural stability were analyzed. Study results indicated limited acute effects from exposure to chlorpyrifos using urinary TCP as a measure of current exposure. The effects occurred primarily on measures of postural sway in the eyes closed and soft-surface conditions, which suggests a possible subclinical effect involving the proprioceptive and vestibular systems. Several other tests of motor and sensory functions did not show any evidence of acute exposure effects, although statistically significant effects of urinary TCP on the Lanthony color vision test scores and one contrast sensitivity test score were found. The visual measures, however, were not significant when a step-down Bonferroni correction was applied. Information also is presented on the sensitivity of the measures to detect effects in an occupationally exposed population using standard error of the parameter estimates.

Animals↗

Neurobehavioral test performance in the third National Health and Nutrition Examination Survey.

The third National Health and Nutrition Examination Survey (NHANES III) contained three computerized neurobehavioral tests from the Neurobehavioral Evaluation System (NES): simple reaction time, symbol-digit substitution and serial digit learning. The neurobehavioral data that were collected came from a nationally representative sample of adults 20-59 years old. Performance on the tests was related to sex, age, education level, family income and race-ethnicity. Performance decreased as age increased, and increased as education level and family income increased. Differences in performance between sexes, levels of education and racial-ethnic groups tended to decrease as family income increased. The relationship between age and performance on the symbol-digit substitution test varied by education level and by racial-ethnic group. The relationship between age and performance on the serial digit learning test varied by racial-ethnic group. Questionnaire variables that were related to performance on one or more of the tests included the reported amount of last night's sleep, energy level, computer or video game familiarity, alcoholic beverages within the last 3 h and effort. Persons who took the tests in English or Spanish performed differently on the symbol-digit substitution and serial digit learning tests. Performance on all the tests decreased as test room temperature increased.

Adult↗

Paternal exposure of rabbits to lead: behavioral deficits in offspring.

Paternal exposures to exogenous agents have been reported to produce a variety of developmental defects in the offspring. In experimental animals, these effects include decreased litter size and weight, increased stillbirth and neonatal death, birth defects, tumors, and functional/behavioral abnormalities-some of these effects being transmitted to the second and third generations. The majority of experimental studies assessing nervous system function of offspring following paternal exposures have utilized rats as the experimental animal, but other species can be used. The National Toxicology Program (NTP) has initiated studies to validate the rabbit as an animal model for human reproductive toxicity, because rabbits are the smallest laboratory animal from which ejaculates can be collected repeatedly. An important part of reproductive toxicology is assessment of the reproductive ability of males following exposure, as well as developmental and functional assessment of their offspring. This article describes a pilot study and a main study to investigate the feasibility of using rabbits to assess the functional effects of paternal exposure to lead. The pilot study included seven male rabbits per group exposed for 15 weeks to lead acetate sufficient to produce 0, 50, or 110 micrograms/dl blood lead. The main study included 15 male rabbits per group exposed for 15 weeks to lead acetate to produce 0, 20, 40, and 80 micrograms/dl blood lead. At the conclusion of the exposure, male rabbits were mated with unexposed females. These females carried their litters to term, delivered, and reared their own offspring. The offspring were weighed at 5, 10, 15, 20, 25, 30, and some at 35 days of age. They were also tested for exploratory activity in a standard figure-eight "maze" for 30 min/day on days 15, 20, 25, and 30. A second assessment of exploratory behavior, along with a simple test of aversive conditioning, was attempted in the pilot study, but was judged not to be suitable for the main study. Of the 21 male rabbits that were mated in the pilot study, 16 produced viable litters (6/7, 6/7, and 4/7 in control, low- and high-lead groups, respectively), with a mean number of 6 live births/litter in each treatment group (range 2-8). Of the 60 rabbits mated in the main study, 57 produced litters, and two rabbits died giving birth. Significant postnatal deaths were observed in all groups, with about one half of the offspring dying before testing was initiated at day 15. There were no treatment-related effects on offspring weight gain through wearing. The data suggest that paternal lead exposure of rabbits may reduce figure-eight activity on day 25, the time of peak activity in the offspring.

Analysis of Variance↗

Evaluation of tremor in aluminum production workers.

A cross-sectional study of 63 current and former aluminum potroom workers and 37 comparison workers was conducted to evaluate for evidence of neurological dysfunction, including tremor from long-term exposures to aluminum using sensitive quantitative measures of arm/hand and leg tremor. Signs of upper extremity tremor were also evaluated by neurological examination and compared with the quantitative measures of arm/hand tremor. Both arm/hand and leg tremor were measured using fatiguing test conditions, but no statistically significant differences due to exposure to aluminum were present between the potroom workers and the comparison workers. The neurological examination also showed no statistically significant differences between the groups on the evaluation of signs of tremor. These results do not support the findings of Best-Pettersen et al., who reported evidence of increased tremor in aluminum workers using the static steadiness test in the Halstead-Reitan battery. Differences between the studies that may have contributed to the contrasting results are discussed. In addition, techniques are presented for using microcomputer-controlled devices to evaluate tremor in both the visible (1-6 Hz) and nonvisible (7-18 Hz) frequencies of the tremor spectrum.

Aluminum↗

Developmental toxicology of industrial alcohols: a summary of 13 alcohols administered by inhalation to rats.

The developmental toxicology of 13 industrial alcohols (methanol, ethanol, 1-propanol, isopropanol, 1-butanol, 2-butanol, tertiary-butanol, 1-pentanol, 1-hexanol, 2-ethyl-1-hexanol, 1-octanol, 1-nonanol, and 1-decanol), and the behavioral teratogenicity of 4 of these alcohols, were assessed in a series of experiments. The results of individual alcohols have been published previously, but the present paper summarizes the results in view of structure-activity relationships among these alcohols. The alcohols were administered by inhalation for 7 hours per day (6 hours/day for 1-decanol) on gestation days 1-19 to groups of approximately 15 pregnant Sprague-Dawley rats. For developmental toxicology evaluations, dams were sacrificed on gestation day 20. Fetuses were serially removed, weighed, sexed, and examined for external malformations. The frequency of visceral malformations and variations was determined in one-half of the fetuses, and the frequency of skeletal deviations was determined in the other half. Behavioral teratology endpoints were investigated in groups of 15 pregnant rats exposed to one of four alcohols (ethanol, 1-propanol, 1-butanol, and tertiary-butanol) and also involved groups of 18 male rats which were exposed to the same concentrations of each alcohol for 6 weeks, and then mated to untreated females. In the behavioral teratology evaluations, all litters were culled to eight pups and fostered to unexposed mothers. Offspring were tested from days 10-90 on a series of behavioral tests designed to evaluate neuromotor integrity, activity levels, learning, and memory. Additionally, brains were removed from 10 offspring per group at 21 days of age, and were dissected into cerebrum, cerebellum, brainstem, and midbrain; these samples were assayed for steady-state levels of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine (serotonin), substance P, B-endorphin, and met-enkephalin. Congenital malformations were noted for methanol, 1-propanol, isopropanol, and 1-butanol, but only at concentrations in excess of 5000 ppm. These concentrations also produced toxicity in the maternal animals; thus, there was little evidence of selective developmental toxicity among the alcohols. Although sporadic behavioral and neurochemical deviations were detected, no consistent pattern of effects was seen for any of the alcohols we tested. It should be noted that alcohols with chain lengths longer than the butyl series could not be generated as vapors at sufficiently high concentrations to produce observable toxicity in the maternal animals. This limits the generality of these findings to the possible developmental effects of these alcohols when taken through other routes of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗