Plasma and blood lead concentrations, lead absorption, and lead excretion in nonhuman primates

The effects of pH, temperature, block of energy production, calcium/calmodulin, protein phosphorylation, and cytoskeleton-disrupting agents (cytochalasin D, nocodazole) on the integrity of the membrane skeleton were studied in polarized MDCK cells. The intracellular distributions of alpha-fodrin, actin, and ankyrin were monitored by immunofluorescence microscopy. The membrane skeleton, once assembled, seemed to be quite stable; the only factors releasing alpha-fodrin from the lateral walls were the acidification of the cytoplasm and the depletion of extracellular calcium ions. Upon cellular acidification, some actin was also released from its normal location along the lateral walls and was seen in colocalization with alpha-fodrin in the cytoplasm, whereas ankyrin remained associated with the lateral walls. No accumulation of plasma membrane lipids was observed in the cytoplasm of acidified cells, as visualized by TMA-DPH. These results suggest that the linkages between the fodrin-actin complex and its membrane association sites are broken upon acidification. The pH-induced change in alpha-fodrin localization was reversible upon restoring the normal pH. Reassembly of the membrane skeleton, however, required temperatures above +20 degrees C, normal energy production, proper cell-cell contacts, and polymerized actin. Release of alpha-fodrin from the lateral walls to the cytoplasm was also observed upon depletion of extracellular calcium ions. This change was accompanied by the disruption of cell-cell contacts, supporting the role of proper cell-cell contacts in the maintenance of the membrane skeleton polarity. These results suggest that local alterations of the cytoplasmic pH and calcium ion concentration may be important in regulating the integrity of the membrane skeleton.     

Intermodality, retrospective image registration in the thorax

The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.     

Evaluation of the protracted stress in the esophageal mucosa of rats

The effect of protracted stress upon the DNA synthesis of the esophageal mucosa of the rat was investigated at various time intervals ranging from one to 56 days. A total of 80 Sprague-Dawley rats were investigated. Lots of 25 rats each were either shock-plunged, subjected to swimming in large basins for two hours or were only transported to the swimming laboratory and used as controls. The remaining 5 rats were non-transported (resting) controls. At the end of the above described procedures, all 80 rats received an intraperitoneal injection of 1 microCi3H-thymidine/gr bodyweight. one hour later the rats were killed. Half of the esophagus was processed for DNA extraction and the other half for autoradiography. When compared to day 0 (resting control rats), the DNA values in experimental animals had increased significantly at day 1, decreased significantly at day 7 in swimming rats and risen once again in both experimental groups at day 14 and more notably at day 28. By 56 days, the values had reached those of day 0. When compared to transported controls at each time interval, both experimental groups had significantly higher DNA values at day 1, significantly lower at day 7 and once again, significantly higher at day 28. Autoradiographic studies of plunged rats showed similar fluctuations in the percentage of labelled basal-parabasal cells in the esophageal mucosa at the various time intervals. The results of this work are similar to those reported previously for the gastric mucosa, the duodenal mucosa and the colonic mucosa of rats subjected to the same stressors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relaxin and decidualization in mice: a reappraisal

The nature of the physiological stimulus inducing decidualization in the endometrium is unknown. In this study we attempted to verify a recent report that relaxin can induce decidualization in intact mice primed with a high dose of estradiol valerate (5 micrograms) and a low dose (10 micrograms) of medroxyprogesterone acetate. In our study, neither s.c. nor intrauterine relaxin, nor intraluminal arachis oil, (an established deciduogenic stimulus) were able to induce decidualization. In addition, while oil was able to induce decidualization (increased uterine weight, and positive Pontamine Sky Blue and stromal alkaline phosphatase reactions) in ovariectomized mice treated with a regimen of estradiol and medroxyprogesterone acetate designed to produce optimum uterine sensitivity, no decidualization occurred in response to either s.c. or intraluminal relaxin. This study fails to provide any support for a role for relaxin as a deciduogenic stimulus.     

Protective role of gamma interferon during the recall response to influenza virus

During secondary immune responses to influenza virus, virus-specific T memory cells are a major source of gamma interferon (IFN-gamma). We assessed the contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68 (H3N2) virus. The IFN-gamma-/- mice displayed significantly reduced survival rates subsequent to a challenge with various doses of the A/WSN/33 virus. This was associated with an impaired ability of the IFN-gamma-/- mice to completely clear the pulmonary virus by day 7 after the challenge, although significant reduction of the virus titers was noted. However, the IFN-gamma-/- mice developed type A influenza virus cross-reactive cytotoxic T lymphocytes (CTLs) similar to the wild-type mice, as demonstrated by both cytotoxicity and a limiting-dilution assay for the estimation of CTL precursor frequency. The pulmonary recruitment of T cells in IFN-gamma-/- mice was not dramatically affected, and the percentage of CD4(+) and CD8(+) T cells was similar to that of wild-type mice. The T cells from IFN-gamma-/- mice did not display a significant switch toward a Th2 profile. Furthermore, the IFN-gamma-/- mice retained the ability to mount significant titers of WSN and HK virus-specific hemagglutination-inhibiting antibodies. Together, these results are consistent with a protective role of IFN-gamma during the heterologous response against influenza virus independently of the generation and local recruitment of cross-reactive CTLs.     

Physical fitness, physical activity, and functional limitation in adults aged 40 and older

PURPOSE: A cohort of middle-aged and older men and women were followed for an average of 5.5 yr to examine the association between physical fitness, physical activity, and the prevalence of functional limitation. METHODS: The participants received medical assessments between 1980 and 1988 and responded to a mail-back survey regarding functional status in 1990. RESULTS: Among 3495 men and 1175 women over 40 yr of age at baseline, 350 (7.5%) reported at least one functional limitation in daily or household activities at follow-up. The prevalence of functional limitation was higher among women than men. Physically fit and physically active participants reported less functional limitation than unfit or sedentary participants. After controlling for age and other risk factors, the prevalence of functional limitation was lower for both moderately fit (odds ratio = 0.4, 95% CI = 0.2-0.6) and high fit men (odds ratio = 0.3, 95% CI = 0.2-0.4), compared with low fit men. Corresponding figures for women were 0.5 (0.3-0.7) and 0.3 (0.2-0.5) for moderately fit and high fit women. The association between physical activity and functional limitation was similar to the data for physical fitness. CONCLUSIONS: These data support a protective effect of physical fitness and physical activity on functional limitation among older adults and extend this protective effect to middle-aged men and women.     

Slow cellular dynamics in MDCK and R5 cells monitored by time-lapse atomic force microscopy

We have examined dynamic events that occur on a time scale of minutes in an epithelial monolayer of Madine-Darby Canine Kidney (MDCK) cells and in ras-transformed MDCK cells by atomic force microscopy (AFM). Cells were imaged under physiological conditions, and time-lapse movies representing approximately 60 s real time per frame were assembled. In normal MDCK cells, two types of protrusions in the apical plasma membrane exhibit dynamic behavior. First, smooth bulges formed transiently over the time scale of minutes to tens of minutes. Second, spike-like protrusions appear initially as bulges, extend well above the apical surface and, finally, seem to detach. R5, an oncogenic transformant derived from MDCK cells, grows very flat on glass. During AFM imaging, these cells sometimes round up and detach from the substrate. In light microscopic observations of parallel preparations, cells rarely detach, suggesting that this is an active response of these cells to irritation by the AFM tip. R5 cells often extend processes that are supported by actin stress fibers. During imaging with the AFM, these processes withdraw at a rate of 1-5 microns/min, similar to that observed by light microscopy. During the withdrawal, movement of the stress fibers can be clearly seen. In the flat periphery of these cells, the transport of intracellular particles along cytoskeletal elements was seen. In addition, we have observed two types of wave-like movements through the cell, which appear to be an organized rearrangement of cytoplasm. One type of wave moves radially out from center of the cell while the other moves circularly along the cell periphery.     

Hemispheric contributions to the integration of visual and auditory information in speech perception

Differential hemispheric contributions to the perceptual phenomenon known as the McGurk effect were examined in normal subjects, 1 callosotomy patient, and 4 patients with intractable epilepsy. Twenty-five right-handed subjects were more likely to demonstrate an influence of a mouthed word on identification of a dubbed acoustic word when the speaker's face was lateralized to the LVF as compared with the RVF. In contrast, display of printed response alternatives in the RVF elicited a greater percentage of McGurk responses than display in the LVF. Visual field differences were absent in a group of 15 left-handed subjects. These results suggest that in right-handers, the two hemispheres may make distinct contributions to the McGurk effect. The callosotomy patient demonstrated reliable McGurk effects, but at a lower rate than the normal subjects and the epileptic control subjects. These data support the view that both the right and left hemisphere can make significant contributions to the McGurk effect.