The morphogenesis of testicular degeneration induced in rats by orally administered 2,5-hexanedione

The neurotoxic hexacarbon 2,5-hexanedione (2,5-HD) produces testicular atrophy in experimental animals. To examine the morphogenesis of the testicular lesion, 1.0% 2,5-HD was provided in the drinking water of adult F-344 rats for up to 6 weeks. After 3 weeks of administration, there were occasional large vacuoles in the basal region of the germinal epithelium. At 4 weeks, these vacuoles were much larger and more numerous; electron microscopy demonstrated that they were derived from the smooth endoplasmic reticulum. The vacuoles were preferentially associated with stages 12, 13, 14, and 1 of the spermatogenic cycle. Additionally, at 4 weeks there was a significant decrease in the number of tubules in stages 7 and 13, and a concomitant increase in the percentage of tubules in stages 3, 5, and 6. By Week 5, most Golgi-phase and cap-phase spermatids were visibly affected, showing margination of nuclear chromatin, and were becoming dissociated from Sertoli cells. Frequent multinucleated giant cells were seen and electron microscopy of these cells suggested that they were derived from fused spermatocytes or spermatids. After 6 weeks, fewer giant cells were present, most tubules contained cellular debris, and many showed empty lumina encircled by a thin ring of cytoplasm near the basement membrane. Interstitial tissue appeared unaffected. These studies indicate that the Sertoli cell is probably an initial target for 2,5-HD action in the testis.     

Mathematical Modeling of the Human Body During Water Replacement and Dehydration: Body Water Changes

A model of the human body that integrates the variables involved in temperature regulation and blood gas transport within the cardiovascular and respiratory systems is presented here. It expands upon previous work to describe the competition between skin and muscles when both require increased blood flows during exercise and/or heat stress. First, a detailed study of the control relations used to predict skin blood flow was undertaken. Four other control relations employed in the model were also examined and modified as indicated by empirical results found in literature. Internal responses to exercise and/or heat stress can affect both thermoregulation and the cardiorespiratory system. Dehydration was studied in addition to complete water replacement during similar environmental and exercise situations. Control relations for skin blood flow and evaporative heat loss were modified and a water balance was added to study how the loss of water through sweat can be limiting. Runoff from sweating as a function of relative humidity was introduced along with evaporation, and these results were compared to data to validate the model. © 2000 Biomedical Engineering Society. PAC00: 8719Pp, 8719Uv, 8719Ff, 8710+e     

Double nondisjunction during karyotypic progression of chemically induced Syrian hamster cell lines

The karyotypic evolution of three chemically induced cell lines of Syrian hamster embryo in culture are described. The only karyotypic alteration of one clone was a trisomy of chromosome #11, which presumably arose by nondisjunction after carcinogen treatment. A pure population of cells with the trisomy was observed repeatedly upon karyotyping of cells at the first three passages after cloning. However, at a late passage, apparently normal diploid cells appeared in the culture, which we propose resulted from a second nondisjunction of one chromosome #11, reverting the cells from trisomy 11 to disomy 11. The karyotypic evolution of two other cell lines also involved double nondisjunction, which resulted in duplication of a translocated chromosome and concurrent loss of the normal nonrearranged chromosome. Taken together with the reported findings of others, the results indicate that double nondisjunction is a mechanism in karyotypic progression during neoplastic development.     

Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis

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Differential effects of two types of environmental novelty on activity and sleep in BALB/cJ and C57BL/6J mice

Change in the sleeping environment can produce significant alterations in sleep. To determine how these alterations may vary with the amount of change and the relative reactivity of the sleeper, we examined the influences of environmental novelty on sleep in two mouse strains that differ in behavioral anxiety. Mice [BALB/cJ (n=7) and C57BL/6J (n=8)] were implanted for recording EEG and activity via telemetry. Following baseline data collection, activity and sleep were examined over 46 h after routine cage change, after placing a simple novel object (PVC Tee) in the home cage, and after handling controls. Mice of both strains showed immediate increases in activity and decreases in rapid eye movement sleep (REM) and non-REM (NREM) after cage change and novel object. Within strain, changes in activity and sleep were greater after cage change than after novel object. Changes in activity and sleep time were significantly correlated in each strain. Compared to C57BL/6J mice, BALB/cJ mice exhibited greater and longer duration initial reductions in sleep time, and greater increases in EEG slow wave activity power after cage change and novel object, but these changes were not followed with subsequent increases in sleep time. In contrast, C57BL/6J mice showed significantly greater subsequent increases in sleep time following the initial reductions induced by both manipulations. The results suggest that initial decreases and subsequent increases in sleep time are related to putative differences in the intensity of environmental novelty (cage change>novel object) and to previously described strain differences in anxiety (BALB/cJ>C57BL/6J).     

Water diffusion in the different microenvironments of breast cancer

The parameters that characterize the intricate water diffusion in tumors may serve to reveal their distinct pathology. Specifically, the application of diffusion magnetic resonance imaging (MRI) can aid in characterizing breast cancer, as well as monitoring response to therapy. We present here a non-invasive, quantitative MRI investigation, at high spatial resolution, of water diffusion in hormonal dependent MCF7 breast tumors implanted orthotopically in immunodeficient mice. Distinctive MRI protocols were designed in this study, utilizing a broad range of diffusion times and diffusion gradient strengths. Application of these protocols allowed water diffusion in the tissue extracellular and intracellular compartments to be distinguished, and the effect of restricted diffusion and water exchange on the water diffusion in these compartments to be evaluated. Pixel-by-pixel analysis yielded parametric maps of the estimated volume fraction and apparent diffusion coefficient of each compartment. The diffusion of the water in the extracellular microenvironment was approximately two fold slower than that of free water, and in the intracellular compartment was about one order of magnitude slower than that of free water and demonstrated restriction of water diffusion at long diffusion times. Mapping of the water fraction in each compartment was further employed to monitor changes during tumor progression and to assess tumor response to hormonal manipulation with a new antiestrogenic drug, tamoxifen methiodide (TMI). It was found that, in parallel to the growth arrest by this drug, the volume fraction of the slowly diffusing water increased, suggesting a TMI-induced cell swelling. This study can serve as a basis for extending diffusion breast MRI in the clinical setting.     

Enhanced zinc consumption causes memory deficits and increased brain levels of zinc

Zinc deficiency has been shown to impair cognitive functioning, but little work has been done on the effects of elevated zinc. This research examined the effect on memory of raising Sprague-Dawley rats on enhanced levels of zinc (10 ppm ZnCO3; 0.153 mM) in the drinking water for periods of 3 or 9 months, both pre- and postnatally. Controls were raised on lab water. Memory was tested in a series of Morris Water Maze (MWM) experiments, and zinc-treated rats were found to have impairments in both reference and working memory. They were significantly slower to find a stationary platform and showed greater thigmotaxicity, a measure of anxiety. On a working memory task, where the platform was moved each day, zinc-treated animals had longer latencies over both trials and days, swam further from the platform, and showed greater thigmotaxicity. On trials using an Atlantis platform, which remained in one place but was lowered on probe trials, the zinc-treated animals had significantly fewer platform crossings, spent less time in the target quadrant, and did not swim as close to the platform position. They had significantly greater latency on nonprobe trials. Microprobe synchrotron X-ray fluorescence (microSXRF) confirmed that brain zinc levels were increased by adding ZnCO3 to the drinking water. These data show that long-term dietary administration of zinc can lead to impairments in cognitive function.     

Extensive training in a maze task reduces neurogenesis in the adult rat dentate gyrus probably as a result of stress

It has recently been shown that hippocampal neurogenesis can be modulated either directly or indirectly by ascending cholinergic inputs from the basal forebrain. In the present work, we sought to address whether extended training in a spatial navigation task would affect hippocampal neurogenesis in the presence of a severe and selective cholinergic depletion. Young female rats received stereotaxic injections of the immunotoxin 192 IgG-saporin into the basal forebrain nuclei and/or the cerebellar cortex. Starting from 4 to 5 weeks post-lesion, and for the subsequent 2 weeks, the animals were trained on paradigms of reference and working memory in the water maze and received single daily i.p. injections of bromodeoxyuridine (BrdU) at the end of each testing session. In line with previous observations, a dramatic 80% decrease in neuron proliferation was seen in the dentate gyrus of lesioned animals, as compared to vehicle-injected or intact controls. Interestingly, however, rats subjected to maze training over 2 weeks, irrespective of their learning success, exhibited significantly fewer newborn neurons than matched controls with no maze exposure. Thus, at least for the type of task used here, which has previously been shown to impose a certain degree of stress, extended training and learning does not appear to affect proliferation in the dentate gyrus.     

Effect of atropine on the bronchial response of asthmatic subjects to the inhalation of ultrasonically nebulized distilled water

To determine whether atropine provides protection against the bronchoconstriction that develops in asthmatic subjects after inhalation of ultrasonically nebulized distilled water, we exposed six asthmatic patients to this stimulus with and without pretreatment with atropine (0.04 mg/kg). The mean FEV1 decreased from 3.32 to 2.39 L (-28%) without and from 3.49 to 3.18 L (-9%) with atropine. This protective effect was statistically significant (p less than 0.05), suggesting that cholinergic pathways are involved in the obstructive response to the inhalation of ultrasonically nebulized distilled water.     

Infrared-spectrometric determination of D2O in biological fluids

The determination of D₂O in biological fluids by means of infrared spectrometry was reinvestigated. When the temperature of a solution, containing D₂O in the range from natural abundance to 5 ml·1^–1 increases, its absorbance decreases and the wavenumber of maximum absorption shifts to a higher value. Both changes are linearly related to the change in temperature. Storage for 17 d in either glass or polyethylene tubes does not affect the D₂O concentration. Purification of biological fluids by vacuum-sublimation removes all substances which also absorb at the O-D vibration band and the recovery of D₂O from plasma and urine is complete. The partition ratio of D₂O between plasma water and red cell water equals unity, and the same holds for plasma water and urine water over a wide range of urine flows and osmolalities. The arterial and urinary disappearance curves of D₂O, measured over several days, both permit the calculation of the total amount of body water (V ^bw), the daily water turn-over (F) and the half-time of water in the body (t _1/2), but the data derived from arterial disappearance curves are more precise. In 16 male mongrel dogs (25–32 kg body mass) the following results were obtained:V ^bw=626±28 ml·kg^–1,F=12.0±3.2% andt _1/2=6.21±1.78 d.