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Biomedical subjects

A Meltzer

Publications and source records attributed to A Meltzer.

At least 19 recordsLinked to original sources
PubMed2002

Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, where family data support substantial heritability.(1) To date, association studies focussed mainly on genes regulating dopaminergic neurotransmission.(2)Interleukin-1 (IL-1) activity in the brain has been implicated with differentiation of dopaminergic neurons(3,4) and modulation of central monoaminergic reactivity.(5) We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) polymorphism,(6) in a sample of 86 children with DSM-IV ADHD and their parents. Transmission disequilibrium analysis showed increased transmission of the IL-1Ra 4-repeat allele (chi(2) = 4.07, P = 0.04) and decreased transmission of the 2-repeat allele (chi(2) = 4.59, P = 0.03) to affected children. The 4-repeat allele was associated with a significantly increased risk for ADHD (chi(2) = 4.46, df 1, P = 0.035, RR = 1.292, 95% CI 1.01-1.66). The IL-1Ra 2-repeat allele was associated with a significantly decreased risk for ADHD (chi(2) = 4.65, df 1, P = 0.03, RR = 0.763, 95% CI 0.59-0.98). If replicated, this finding may point to a role for brain cytokine activity in the etiopathogenesis of ADHD.

Adolescent↗
PubMed1998

Testosterone concentrations, testes weight and morphology of mule drakes (Muscovy drake x Khaki Campbell).

1. Mule ducks were produced by naturally mating Muscovy drakes and Khaki Campbell ducks. 2. Semen was collected from 6-month-old mule drakes via an artificial vagina. The fluid was clear without any spermatozoa or spermatids. 3. Testes from 27-week-old mule drakes were smaller in size than those of Khaki Campbell drakes but heavier than Muscovy males of the same age. Histological sections of these testes revealed that spermatogenesis was not complete. 4. Testosterone concentration in the mule drakes was higher than in Muscovy males but similar to Khaki Campbell drakes. 5. Mule drakes have strong sexual drives as a result of high concentrations of testosterone, but, because spermatogenesis is incomplete, their semen had no sperm.

Aging↗
PubMed1996

Cellular and secretory mechanisms related to delayed radiation-induced microvessel dysfunction in the spinal cord of rats.

PURPOSE: This study aimed to investigate long-term, radiation-induced changes in microvessel permeability, the profile of the vasoactive mediators endothelin and nitric oxide, and the response of specific cell systems in the irradiated spinal cord of rats. METHODS AND MATERIALS: The thoracolumbar spinal cords of Fischer rats were irradiated to a dose of 15 Gy, and the rats were sacrificed at various times afterward. Endothelin levels and nitric oxide-synthase (NOS) activity were assayed in extracts of spinal cords. Microvascular permeability and the effect of treatment with recombinant human manganese superoxide dismutase (r-hMnSOD) were assessed quantitatively. Immunohistochemistry evaluated astrocytes, microglia, vascular basal membrane, and neurofilaments. RESULTS: None of the rats developed neurologic dysfunction. Endothelin levels were significantly reduced at 18 h after irradiation and markedly attenuated after 10 days (p < 0.007). Thereafter, endothelin levels returned to normal values at 56 days after radiation and escalated to markedly high levels after 120 and 180 days (p < 0.002). NOS activity remained very low throughout the period of follow-up and failed to counterbalance the shifts in endothelin levels. Treatment with r-hMnSOD had no effect on normal vascular permeability but it abolished the abnormally increased permeability measured at 18 h after radiation and again after 120 and 180 days. Standard microscopic evaluation failed to reveal abnormalities in the irradiated spinal cord, but immunohistochemical staining showed a progressive increase in the number of microglial cells per field after 120 and 180 days (p < 0003). A similar increase in the number of astrocytic cells per field was noted after more than 180 days, but an earlier short lasting peak was also noted at 14 days after radiation. No abnormalities were found in blood vessel configuration, density, diameter, and basal membrane staining, or in the neurofilaments. CONCLUSION: Marked imbalance in the regulatory function of endothelium-derived mediators of the vascular tone is present after radiation therapy probably inducing chronic vasoconstriction. This imbalance favors localized procoagulation that may enhance the consequent loss of function measured as increased permeability. Microglial proliferation may account for continuous release of superoxide that may enhance disruption of normal permeability. The latter is corrected by SOD treatment. Astrocytic proliferation may present a response to the mitogenic effect of endothelin and to microglial-derived paracrine effect of cytokines.

Animals↗
PubMed1996

DNA--protein crosslinks, a biomarker of exposure to formaldehyde--in vitro and in vivo studies.

Formaldehyde (FA) is a widely produced industrial chemical. Sufficient evidence exists to consider FA as an animal carcinogen. In humans the evidence is not conclusive. DNA-protein crosslinks (DPC) may be one of the early lesions in the carcinogenesis process in cells following exposures to carcinogens. It has been shown in in vitro tests that FA can form DPC. We examined the amount of DPC formation in human white blood cells exposed to FA in vitro and in white blood cells taken from 12 workers exposed to FA and eight controls. We found a significant difference (P = 0.03) in the amount of DPC among exposed (mean +/- SD 28 +/- 5%, minimum 21%, maximum 38%) than among the unexposed controls (mean +/- SD 22 +/- 6%, minimum 16%, maximum 32%). Of the 12 exposed workers, four (33%) showed crosslink values above the upper range of controls. We also found a linear relationship between years of exposure and the amount of DPC. We conclude that our data indicate a possible mechanism of FA carcinogenicity in humans and that DPC can be used as a method for biological monitoring of exposure to FA.

Biomarkers↗
PubMed1996

Biological monitoring of exposure to cadmium, a human carcinogen, as a result of active and passive smoking.

Cadmium (Cd), a known human carcinogen, is one of the components of tobacco and also has many industrial uses. Smoking Cd-contaminated cigarettes at work may cause an increase in blood levels and toxicity of Cd. For a population of nonexposed workers, we compared blood Cd and urine cotinine (Cot) levels as biological markers of exposure to cigarette smoke of active smokers (AS) and passive smokers (PS) with those of unexposed nonsmokers (UNS) in 158 workers. The mean Cd in AS (0.097 microgram%; ie, 0.097 microgram/100 mL whole blood) was significantly higher than in UNS (0.085 microgram%), and was very close to the mean Cd levels in PS (0.093 microgram%). Mean Cd levels in exposed past smokers (0.105 microgram% was higher than in nonexposed past smokers (P < 0.05) and in AS. The mean Cot level was significantly higher in AS than in PS or in UNS. Increased smoking was associated directly with increased blood Cd and urine Cot. Our results supported and proved quantitatively that exposure to cigarette smoke is harmful to both AS and PS, as we show that in both cases there is an increase in blood Cd. According to our results, exposure to cigarette smoke via active and passive smoking increases blood Cd by an average of 0.01 micrograms% over the background (UNS). We conclude that exposure to cigarette smoke is a confounder to be taken into account when carrying out epidemiological studies and surveillance programs on workers exposed to Cd at work.

Biomarkers↗
PubMed1991

Cultured human atherosclerotic plaque smooth muscle cells retain transforming potential and display enhanced expression of the myc protooncogene.

The proliferation of vascular smooth muscle cells (SMC) is critical to atherosclerotic plaque formation. The monoclonal hypothesis proposes that the stimulus for this SMC proliferation is a mutational event. Here we describe a procedure for growing human plaque smooth muscle cells (p-SMC) in culture. We show that p-SMCs derived from two patients differ from SMC cultured from normal vascular tissue in expression of the protooncogene myc. One p-SMC strain was extensively characterized; these diploid, karyotypically normal cells have a finite life span in culture. Ultrastructural examination revealed two populations, one with classic contractile SMC appearance, the other, modulated to a synthetic state. Northern blotting showed a 2- to 6-fold and a 6- to 11-fold enhanced expression of myc by p-SMC, compared to SMC derived from healthy human aorta (HA-SMC) and saphenous vein (HV-SMC), respectively. In contrast, the p-SMC and HV-SMC expressed similar levels of message for the genes N-myc, L-myc, Ha-ras, fos, sis, myb, LDL receptor, EGF receptor, IGF I receptor, IGF II, and HMG CoA reductase. Finally, although p-SMCs are not tumorigenic, DNA isolated from these cells is positive in the transfection-nude mouse tumor assay. Myc, however, does not appear to be the transforming gene because no newly introduced human myc gene was detected in the p-SMC-associated nude mouse tumor. Thus human atherosclerotic p-SMCs possess both an activated myc gene and a transforming gene that is retained throughout many cell passages.

Animals↗
PubMed1990

Dormancy and breast cancer.

A case is presented in which multiple nodules of recurrent cancer appeared about the scar 25 years after radical mastectomy. They were accompanied by an inflammatory reaction. Breast cancers may recur as long as 50 years after surgery. Such late recurrence is accomplished by the cancer cell entering a "dormant" state in which little or no de novo DNA transcription occurs and only enough RNA is translated into proteins to maintain the vegetative functions that sustain cell viability. Features favoring the evolvement of dormancy are discussed as well as the nature of the cocoon-like shell which affords such cancer cells protection from the host's cellular and serological defenses. Speculation, promoted by the new cellular biology, as to the cause of secondary inflammatory cancers, is presented. A possible mechanism for the reactivation of these quiescent cells is suggested. The altered immune reactions of host and cancer cells provide an explanation for the controversies plaguing surgeons regarding the treatment and prognosis of breast cancer.

Breast Neoplasms↗
PubMed1990

The effect of tamoxifen on sexual puberty of turkey toms and Muscovy drakes.

The effects of Tamoxifen (TAM) on reproductive traits in young turkey toms and Muscovy drakes were studied. At 6 wk of age, five toms were injected every other day with 1 mg TAM/kg BW, while six others were treated with corn oil (controls). In the toms, using TAM advanced semen production by 4 wk (13.5 versus 17.5 wk of age) and increased the size of the snood and testes. Similarly, in the Muscovy drake, using TAM enhanced penis growth and advanced semen production by 5 wk.

Animals↗
PubMed1988

Oxygen consumption of a terrestrial toad (Bufo viridis) and semi-aquatic frog (Rana ridibunda).

1. Oxygen consumption was measured before and after dehydration at different ambient temperatures (Ta) in the terrestrial toad Bufo viridis and the semi-aquatic frog Rana ridibunda. 2. The metabolic rates at Tas between 14 and 27 degrees C were almost the same for R. ridibunda and B. viridis. 3. The metabolic rate at higher Tas (between 27 and 36 degrees C) was higher in R. ridibunda than in B. viridis. This situation was found before and after dehydration. 4. A similar situation was found with CO2 production, which was higher at high Tas in R. ridibunda compared with B. viridis.

Animals↗
PubMed1987

Interrelationship between metabolism of tritiated water, 22sodium and dry matter intake by beef cattle consuming wheat straw and poultry litter in free choice.

1. Metabolism of tritiated water and 22sodium was studied in six beef cows under Mediterranean summer conditions in order to find whether the turnover of these tracers can be used to evaluate pasture intake. 2. The diet of the cows included ad libitum access to two components which were given separately in different troughs: one was poultry litter and the other was wheat straw, to simulate the dry pasture. 3. Voluntary daily dry matter intake (111 g/kg0.75) was unexpectedly high considering the low digestibility of the feed. 4. The assumptions of constant ratios of water intake to water turnover and of dry matter intake to water intake were confirmed. Consequently, dry matter intake was determined accurately from water turnover measurements. 5. Sodium intake was practically equal to sodium turnover and most of the sodium secreted in feces was of endogenous origin. 6. Pasture intake can be predicted from sodium turnover once the concentration in feed and water consumed is known.

Animal Feed↗
PubMed1987

Administration-time-dependency of the pharmacokinetic behavior and therapeutic effect of a once-a-day theophylline in asthmatic children.

Using a double-blind, placebo-control, crossover study design, 8 asthmatic children (8-15 years) were evaluated for temporal patterns in airways function throughout separate study periods when treatment was placebo or Theo-24 once-daily on separate occasions at 0600, 1500 or 2100 hr. During 39-hr in-hospital observations, pulmonary function and serum theophylline concentrations (STC) were assessed every 3 hr under all treatments. The pharmacokinetics of Theo-24 varied greatly depending on the dosing time. For the afternoon and evening dosings, the Cmax, Tmax, AUC, % swing, % fluctuation, % AUC fluctuation, % nocturnal excess and Cav(2-6 hr) were all statistically significantly greater than for the morning dosing. Compared with the placebo regimen, dosing patients with Theo-24 at 1500 hr disrupted circadian patterns of airways function, especially airways patency, while dosing at 2100 hr, reduced the amplitude and shifted the acrophase of several spirometric measures to a slightly earlier time. Theo-24 treatment irrespective of dosing time resulted in comparable enhancement of the group 24-hr mean, minimum and maximum values of airways patency with reference to placebo baselines. Theo-24 dosing at 1500 or 2100 hr, however, resulted in the best effect on the airways as assessed by the 24-hr mean FEV 1.0 level in 7 of the 8 asthmatic children. When the drug was given at 1500 hr, the time of lowest FEV 1.0 was shifted from the nighttime hours in 5 of 8 patients. These findings suggest that clinicians need to individualize the theophylline dosing schedule of patients to best control the symptoms of asthma.

Asthma↗
PubMed1986

Efficiency of effect of high ambient temperatures on food utilisation in male broilers.

The effect of ambient temperatures above 28 degrees C on the efficiency of food utilisation were studied in 7 consecutive flocks of male broilers, grown in a cross-ventilated controlled environment poultry house. The best correlation between the food:gain ratio and temperature was obtained when the latter was expressed as degrees-h (Th), that is, the aggregate of the differences between the ambient temperature and 28 degrees C, measured hourly. The equation: Food:gain ratio = 2072 + 0.125 X Th, demonstrates clearly the negative effect of high temperatures on food:gain ratio in broilers. It might be helpful for the broiler industry when evaluating the need for and planning of cooling devices for poultry houses.

Animal Nutritional Physiological Phenomena↗