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Biomedical subjects

F J Miller

Publications and source records attributed to F J Miller.

At least 73 records · Page 4Linked to original sources
PubMed1991

Alveolar epithelial cell injuries by subchronic exposure to low concentrations of ozone correlate with cumulative exposure.

Electron microscopy morphometry has been used to study the effects of cumulative exposure of low levels of inhaled O3 on lung proximal alveolar tissue. Six-week-old Fisher 344 rats were exposed to O3 in two different subchronic low-level exposure patterns. The first was a 12 hr/day exposure for 6 weeks and included two O3 concentrations, 0.12 and 0.25 ppm. The second consisted of an exposure profile having a background level of 0.06 ppm with an exposure peak 5 days each week that went from 0.12 to 0.25 ppm and back to 0.12 ppm over a 9-hr period. Rats given the second exposure pattern were exposed for either 3 or 13 weeks. Changes in the volumes of alveolar epithelium were found to be consistent and reproducible markers for cell injury and/or response. Results from the first study indicated that the relative volume of the type I epithelium increased 13 and 23% over the control value (p less than 0.05) following exposures for 6 weeks to 0.12 and 0.25 ppm, respectively. The magnitude of the increases were clearly concentration related. Similarly, when a fixed exposure concentration was employed the relative volume of type I epithelium was found to increase in proportion to the exposure time. In the second exposure, increases of 9 and 33% in relative volume of type I epithelium were found respectively after 3 and 13 weeks of exposure. If the total exposure determined by the product of O3 concentration (including background) and exposure time is plotted against the relative volume of type I epithelium from both the 0.12 ppm (60.5 ppm-hr) and 0.25 ppm (126 ppm-hr) exposures and the 3-week (45.3 ppm-hrs) and 13-week (196.2 ppm-hr) exposures, a linear relationship between increases in type I cell volume and the concentration X time product is observed. The coefficient of correlation (r2) for the linear regression of the animal means is 0.72. Changes in the volume of Type II epithelial cell also correlate with the concentration X time product (r2 = 0.66). This suggests that epithelial cell reactions to low-level subchronic exposure of O3 are directly related to the cumulative oxidant concentration. The pattern of exposure did not appear to affect the resulting degree of injury. Furthermore, a low level of background exposure may contribute to the epithelial cell injuries.

Animals↗
PubMed1991

Routine fluoroscopic cholangiography during laparoscopic cholecystectomy: an argument.

We evaluated the impact of routine fluoroscopic cholangiography on our first 100 laparoscopic cholecystectomies. Catheterization of the cystic duct was successfully performed in 89 of 99 attempts. The cholangiogram altered the course of the procedure in 9 (10%) of these cases. In three subjects, the information obtained revealed unsuspected choledocholithiasis. In the remaining six patients, unusual and potentially hazardous anatomic relationships were discovered that were not visible via laparoscopic exposure alone. Arguments for the selective use of cholangiography during open cholecystectomy are based only on the identification of unsuspected stones. The strongest argument for routine cholangiography during laparoscopic cholecystectomy is the additional anatomic information obtained. Based on our experience, we advocate that routine cholangiography be a part of all laparoscopic cholecystectomies.

Adult↗
PubMed1991

Regional increases in rat nasal epithelial cell proliferation following acute and subchronic inhalation of formaldehyde.

Short-term studies (9 days) in the rat have demonstrated that formaldehyde-induced nasal epithelial lesions are associated with increases in surface epithelial cell proliferation rates. The present studies were designed, in part, to investigate cell proliferation rates in the nasal epithelium of rats exposed to formaldehyde for a longer duration in order to determine if correlations exist between (1) the concentration-response in cell proliferation rate with the previously published formaldehyde bioassay tumor response; (2) sites of increased cell proliferation and the regions of the nasal passages that exhibit formaldehyde-induced cytotoxicity; and (3) sites of increased cell proliferation and the regions of the rat nasal passages previously determined to be most susceptible to neoplasia (i.e., the lateral meatus and nasal septum of the anterior nasal passages). Another important endpoint of this study was to provide data for a comparison of formaldehyde-induced responses in rats with previous findings in rhesus monkeys. Fischer-344 rats were exposed to 0, 0.7, 2, 6, 10, or 15 ppm formaldehyde for up to 6 weeks and pulse labeled with tritiated thymidine prior to each scheduled termination. Exposure to formaldehyde at 6 ppm or higher induced site-specific lesions in the nasal respiratory epithelium and was associated with increases in cell proliferation rate which remained statistically elevated throughout the 6 weeks. While a direct correlation between sites susceptible to formaldehyde-induced nasal cancer and increased cell proliferation was not evident, results from the present studies did demonstrate a clear correlation between sites of cellular injury and increases in cell proliferation and a concentration-dependent response which correlated with the previously published formaldehyde bioassay tumor response. Furthermore, this work demonstrated that formaldehyde-induced responses in rats exposed to 6 ppm were morphologically similar to those reported in the rhesus monkey; however, the distribution of lesions between the two species differed significantly.

Administration, Inhalation↗
PubMed1991

Airway structure variability in the Long-Evans rat lung.

Mathematical models used to study deposition of inhaled toxicants require morphometric data to represent the tracheobronchial airways of laboratory animals. Because of the difficulty and cost of obtaining detailed measurements, morphometric models are generally based on measurements from a small number of specimens. To determine the degree of interanimal variability among laboratory animals of the same strain and size, lengths and diameters of the same 200 airways were measured in solid casts in each of 10 male Long-Evans rats. Intraanimal variability was substantially greater than interanimal variability for airway lengths and diameters. Intraanimal variability was reduced when the airways were grouped so that airway generations were adjusted for lobar position. The study results suggest that detailed measurements of the conducting airways in a small number of casts with summarization techniques that retain lobar information will provide a less variable estimate of lung geometry than a smaller number of measurements made in several casts.

Animals↗
PubMed1991

Percutaneous rotational contact biliary lithotripsy: initial clinical results with the Kensey Nash lithotrite.

The percutaneous rotary lithotrite introduces a new concept to fragmentation and percutaneous removal of gallstones. A fluid vortex is generated, pulling calculi into a high-speed blade that fragments stones to predominantly under 500 microns. The results of treating the first 10 patients with this instrument reveal that large stone burdens as well as small stones (2-3 mm) of any composition can be removed if the gallbladder is of sufficient size to accommodate the six-pronged basket. Rotation times of 7-39 minutes were required. Nine of 10 procedures were completed; access was lost in one case. One major complication occurred. At repeat oral cholecystography, the gallbladder was visualized after 3-6 weeks in eight of the nine patients. Ursodeoxycholic acid was administered from 3 to 12 months to five patients with either residual stones or aggregates. The hospital stay ranged from 48 to 72 hours. All patients (except the patient who underwent surgery) resumed light activity in 3-4 days and strenuous activity and full diet within 3 weeks.

Cholelithiasis↗
PubMed1991

Intraoperative cholangiography: use of portable fluoroscopy and transmitted images.

Intraoperative cholangiograms were obtained with portable fluoroscopy in 53 patients during laparoscopic cholecystectomy, and the images were transmitted to the radiology department. Each image was assessed for diagnostic quality and bile duct abnormalities (eg, retained stones and duct aberrancies). The aberrancy rate was 5.7% with the aberrant duct in the region of surgical dissection. The fluoroscopic technique provided diagnostic images with the advantage of real-time visualization, immediate communication with the surgeon, and the potential to decrease the risk of bile duct injury.

Cholangiography↗
PubMed1991

Activation in the region of parabrachial nucleus elicits neurogenically mediated coronary vasoconstriction.

A role for parabrachial nucleus in cardiovascular regulation is suggested by evidence that electrical stimulation in this region elicits increase in heart rate and arterial pressure. We hypothesized that parabrachial nucleus may also be involved in control of coronary vasomotor tone. After beta-adrenergic receptor blockade in anesthetized cats, electrical stimulation in the region of parabrachial nucleus produced no change in heart rate, an increase in arterial pressure (34 +/- 6 mmHg), and a transient reduction in coronary blood flow velocity (-21 +/- 2%). Coronary resistance (72 +/- 9%) and femoral resistance (189 +/- 31%) increased markedly. The decrease in coronary blood flow velocity was abolished by stellate ganglionectomy or alpha 1-adrenergic blockade without altering pressor or femoral responses. Injection of the neurotransmitter L-glutamate or kainic acid into parabrachial nucleus also elicited coronary vasoconstriction. We conclude that electrical or chemical activation in the region of parabrachial nucleus elicits coronary vasoconstriction as part of a generalized sympathetic activation. The fact that the coronary response is elicited by chemical activation suggests that cell bodies in the region of medial parabrachial nucleus and subceruleus, as opposed to fibers of passage, are involved in this central neural coronary vasoconstriction.

Animals↗
PubMed1991

Inhomogeneity of ventilatory unit volume and its effects on reactive gas uptake.

This study addressed the question of whether variations in the volume of alveoli and alveolar ducts forming single units of ventilation can significantly influence the distribution and uptake of inspired reactive gases. Quantitative serial section analyses of vascular perfusion-fixed rat lungs were used to determine the anatomic dead space proximal to specific ventilatory units as well as the gas volume of these ventilatory units. Three reconstructions, each consisting of ventilatory units distal to a specific bronchus, were carried out. The number of ventilatory units for each reconstruction varied from 26 to 71. The average ventilatory unit volume for the three reconstructions [0.53 +/- .03 (SE) mm3] was not significantly different from measurements based on random sampling. The distribution of ventilatory unit volume was diverse, with 15% of the population having a volume less than 0.3 mm3 and 9% of the population having a volume greater than 1.0 mm3. For a gas of relatively low reactivity (e.g., oxygen) the predicted oxygen uptake per unit surface area did not vary significantly between ventilatory units. The predicted oxygen uptake was approximately 92% of the uptake in the absence of gradients in oxygen concentration between ventilatory units. For a highly reactive gas (e.g., ozone), the predicted uptake per unit surface area in the proximal portions of larger ventilatory units was significantly greater than the average uptake. These results suggest that focal areas of injury likely result from exposure to inhaled reactive gases.

Animals↗
PubMed1991

Percutaneous gallstone lithotripsy. Results in acute and chronic swine models.

The authors describe here a rotary catheter for the percutaneous fragmentation of gallstones. Gallstones are drawn into the rotating impeller by a powerful vortex and mechanically fragmented. Fragments are aspirated from the gallbladder following use of the device. The safety and efficacy of the device was tested after placement of human gallstones in the pig's gallbladder in 19 acute, 15 chronic, and two control experiments. In 27 completed experiments, 206 human gallstones (6-20 mm) were implanted. Most residual fragments were less than 2 mm; 24 fragments were 2 to 4 mm and seven were 5 to 8 mm. Acute histologic changes included focal loss of mucosa, mucosal and submucosal hemorrhage, and deposition of biliary material in the mucosa and submucosa. At 30 and 90 days, gallbladder histology revealed regeneration of the mucosa with isolated granuloma formation.

Acute Disease↗
PubMed1990

2,5-Hexanedione-treated tubulin microinjected into sea urchin zygotes induces mitotic abnormalities.

Zygotes of Lytechinus pictus and Lytechinus variegatus were microinjected with 2,5-hexanedione (2,5-HD)-treated tubulin prior to the first mitotic cycle. Mitotic spindles were small with a well-defined metaphase plate, but poor birefringence and poor astral development. Abnormalities were observed in chromosome movement at anaphase and cytokinesis. Neither microinjections of untreated tubulin or 3-acetyl-2,5-hexanedione-treated tubulin, nor incubation of zygotes in 2,5-HD-containing sea water produced abnormalities. The results can be explained in terms of the nondissociating properties of 2,5-HD-treated tubulin. 2,5-HD-treated tubulin dissociates slowly from microtubules, a property which, besides favoring the formation of stable microtubules, allows this tubulin to induce microtubule assembly when present in substoichiometric amounts. These characteristics have been implicated as a cause of 2,5-HD-induced Sertoli cell dysfunction. The effect of 2,5-HD-treated tubulin on microtubule dynamics in sea urchin zygotes may bear similarities to the effects of 2,5-HD treatment in vivo on Sertoli cell microtubules.

Animals↗
PubMed1990

Protein synthesis and the cell cycle: centrosome reproduction in sea urchin eggs is not under translational control.

The reproduction, or duplication, of the centrosome is an important event in a cell's preparation for mitosis. We sought to determine if centrosome reproduction is regulated by the synthesis and accumulation of cyclin proteins and/or the synthesis of centrosome-specific proteins at each cell cycle. We continuously treat sea urchin eggs, starting before fertilization, with a combination of emetine and anisomycin, drugs that have separate targets in the protein synthetic pathway. These drugs inhibit the postfertilization incorporation of [35S]methionine into precipitable material by 97.3-100%. Autoradiography of SDS-PAGE gels of drug-treated zygotes reveals that [35S]methionine incorporates exclusively into material that does not enter the gel and material that runs at the dye front; no other labeled bands are detected. Fertilization events and syngamy are normal in drug-treated zygotes, but the cell cycle arrests before first mitosis. The sperm aster doubles once in all zygotes to yield two asters. In a variable but significant percentage of zygotes, the asters continue to double. This continued doubling is slower than normal, asynchronous between zygotes, and sometimes asynchronous within individual zygotes. High voltage electron microscopy of serial semithick sections from drug-treated zygotes reveals that 90% of the daughter centrosomes contain two centrioles of normal appearance. From these results, we conclude that centrosome reproduction in sea urchin zygotes is not controlled by the accumulation of cyclin proteins or the synthesis of centrosome-specific proteins at each cell cycle. New centrosomes are assembled from preexisting pools of ready-to-use subunits. Furthermore, our results indicate that centrosomal and nuclear events are regulated by separate pathways.

Animals↗
PubMed1990

Techniques for color flow sonography of the lower extremity.

Color flow sonography permits noninvasive examination of the deep venous system in the lower extremity. In many patients, the modality is sufficiently accurate to serve as the sole diagnostic procedure for suspected deep venous thrombosis. Over 1,500 color flow sonographic examinations of the lower extremity have been performed at our institutions with various scanning techniques. For the inexperienced sonographer, we describe our current technique, which is easy, quick, accurate, and well tolerated by patients.

Color↗
PubMed1990

Symptomatic lower extremity deep venous thrombosis: accuracy, limitations, and role of color duplex flow imaging in diagnosis.

Color duplex flow imaging (CDFI) permits pain- and risk-free direct imaging of the deep venous system of the lower extremities. To prospectively ascertain the accuracy and limitations of this technique, CDFI was performed in 75 lower limbs of 69 consecutive patients referred for venographic evaluation of clinically suspected lower extremity deep venous thrombosis (DVT). The CDFI study was obtained within 24 hours of the contrast venogram. Both studies were interpreted without knowledge of the patient's clinical findings or the results of the other test. Contrast venography was regarded as the standard for diagnosis of DVT. Accuracy was 99% for detection of DVT above the knee and 81% below the knee. Sonographic evaluation of the calf veins was technically adequate in 60% of limbs; accuracy was 98% in this group. In the 40% of limbs with technically limited CDFI studies of the calf, accuracy decreased to 57%. Although small nonocclusive thrombi occurred infrequently in this series of symptomatic patients, CDFI missed three of four such thrombi. It is concluded that CDFI, when not technically compromised, is sufficiently accurate to definitively diagnose symptomatic lower extremity DVT.

Adult↗
PubMed1990

Pulmonary effects due to subchronic exposure to oil fog.

Male and in some cases female rats were exposed to an oil fog generated by flash vaporization and subsequent condensation of light-weight lubricating oil. Exposures were for 3.5 h/d, 4d/wk for 13 wk. Males were exposed at concentrations of 1.5, 0.5, 0.2 or 0.0 mg/l (1500, 500, 200, and 0 mg/m3) and a particle size of approximately 1 micron (mass median aerodynamic diameter). A number of biologic endpoints were assessed the day after the last exposure and, in some cases, after a 4 wk recovery period. Effects of 1.5 mg/l on male and female rats were compared. Diffuse accumulation of macrophages in the alveoli was observed in all oil fog exposed groups. The degree of severity was concentration dependent. Histopathologic changes were more prominent in males than in females and represented the most notable gender-related differences. Histologic effects observed one day and 4 wk post exposure were similar. Minimal histopathologic changes and minimal increase in lavage fluid protein were the only effects observed at the 0.2 mg/l exposure level. There was a significant increase in lavage fluid protein, percent lavagable polymorphonuclear leukocytes and lung wet and dry weight following exposure to both 0.5 and 1.5 mg/l. At the highest exposure concentration effects on lung weights were still evident 4 wk post exposure. Pulmonary function endpoints including total lung capacity, vital capacity, residual volume, diffusing capacity to CO, compliance, and end expiratory volume (EEV) were unaffected by oil fog exposure with the exception of EEV in males exposed at the 1.5 mg/l level. All of the changes observed following oil fog exposure were consistent with a mild inflammatory edema.

Aerosols↗
PubMed1990

The U.S. Environmental Protection Agency's inhalation RfD methodology: risk assessment for air toxics.

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. This paper presents a brief background on the development of the inhalation reference dose (RfDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated into the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extrarespiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.

Administration, Inhalation↗
PubMed1989

Reproductive capacity of sea urchin centrosomes without centrioles.

For animal cells, the relative roles of the centrioles and the pericentriolar material (the centrosomal microtubule organizing center) in controlling the precise doubling of the centrosome before mitosis have not been well defined. To this end we devised an experimental system that allowed us to characterize the capacity of the centrosomal microtubule organizing center to double regularly in the absence of centrioles. Sea urchin eggs were fertilized, stripped of their fertilization envelopes, and fragmented before syngamy. Those activated egg fragments containing just the female pronucleus assembled a monaster at first mitosis. A serial section ultrastructural analysis of such monasters revealed that the radially arrayed microtubules were organized by a hollow fenestrated sphere of electron-dense material, of the same appearance as pericentriolar material, that was devoid of centrioles. We followed individual fragments with only a female pronucleus through at least three cell cycles and found that the monasters did not double between mitoses. The observation that fragments with only a male pronucleus repeatedly divided in a normal fashion indicates that the assembly and behavior of monasters were not artifacts of egg fragmentation. Our results demonstrate that the activity that controls the precise doubling of the centrosome before mitosis is distinct and experimentally separable from the centrosomal microtubule organizing center. Our observations also extend the correlation between the reproductive capacity of a centrosome and the number of centrioles it contains (G Sluder and CL Rieder, 1985a: J. Cell Biol. 100:887-896). For a cell that normally has centrioles, we show that a centrosome without centrioles does not reproduce between mitoses.

Animals↗
PubMed1989

Centrosome inheritance in starfish zygotes: selective loss of the maternal centrosome after fertilization.

The mature egg inherits a centrosome from the second meiotic spindle, and the sperm introduces a second centrosome at fertilization. Since only one of these centrosomes survives to be used in development, specific mechanisms must exist to control centrosome inheritance. To investigate how centrosome inheritance is controlled we used starfish eggs as a model system, because they undergo meiosis after fertilization. As a result, the fate of the maternal and paternal centrosomes can be followed by light microscopy and experimentally manipulated in vivo. We show initially that only the paternal centrosome is used in starfish zygote development; the maternal centrosome retained from meiosis II is functionally lost before first mitosis. We then tested a number of possible ways in which the zygote could exert this differential control over the stability of centrosomes initially residing in the same cytoplasm. The results of these experiments can be summarized as follows: (1) Although the microtubule organizing center activity of the maternal centrosome is not degraded after meiosis, the ability of this centrosome to double at successive mitoses is lost. (2) The sperm centrosome is not "masked" from cytoplasmic conditions which could destabilize all centrosomes during or after the meiotic sequence. (3) The functional loss of the maternal centrosome is not due to its cortical location. (4) The loss of this doubling capacity is determined by the egg, not by putative inhibitory factors from the fertilizing sperm. (5) The destabilization of the maternal centrosome is not due to the complete loss of its centrioles. Together, these results demonstrate that all maternal centrosomes are equivalent and that they are intrinsically different from the paternal centrosome. This intrinsic difference, in concert with a change in cytoplasmic conditions after meiosis, determines the selective loss of the maternal centrosome inherited from the meiosis II spindle.

Animals↗