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D P Penney

Publications and source records attributed to D P Penney.

At least 19 recordsLinked to original sources
PubMed1997

Thresholds for fetal hemorrhages produced by a piezoelectric lithotripter.

Hemorrhage to fetal tissues occurred when late-term pregnant mice were exposed to lithotripter fields of relatively low amplitude. These hemorrhages were always observed in tissues near developing bone or cartilaginous structures such as the head, limbs and ribs, while soft tissues distant from bone were relatively free of hemorrhage. Thresholds for hemorrhage in the fetus were determined for exposures of pregnant mice on the 18th day of gestation to 200 pulses from a piezoelectric lithotripter. Animals were exposed to axial peak positive pressures of either 0 (sham), 1, 2, 3, 5 or 10 MPa. Thresholds for hemorrhage to the head, limbs, ribs and lung were all < 1 MPa.

Animals↗
PubMed1997

Age dependence of ultrasonically induced lung hemorrhage in mice.

Thresholds for ultrasonically induced lung hemorrhage were determined in neonatal mice (24-36 h old), juvenile mice (14 d old) and adult mice (8-10 weeks old) to assess whether or not the threshold for lung hemorrhage is dependent upon age. Ultrasonic exposures were at 1.15 MHz with a pulse length of 10 microseconds, pulse repetition frequency of 100 Hz and a total exposure duration of 3 min. The threshold for lung hemorrhage occurred at a peak positive acoustic pressure of approximately 1 MPa for mice in all three age groups. Although the thresholds were similar for neonatal, juvenile and adult mice, the sizes of the suprathreshold hemorrhages were significantly larger in adult mice than in neonatal or juvenile mice.

Aging↗
PubMed1997

Remnants of Albunex nucleate acoustic cavitation.

Mice were injected with 0.1 mL Albunex and exposed to 200 pulses from a piezoelectric lithotripter at times ranging from 5 min to 24 h following injection. Each pulse was approximately 1.5 sinusoidal oscillations at a fundamental frequency of approximately 0.1 MHz with pressure amplitude of approximately 2 MPa. Although the contrast agent ceases to be an effective scatterer of diagnostic ultrasound after a few minutes in the circulation, the modest lithotripter exposures caused significant hemorrhaging in bladder, mesentery and intestine for periods of up to 4 h after injection. The results demonstrate either that highly stable bubbles much smaller than resonance size or air-containing fragments of the shells of Albunex serve as effective nuclei for acoustic cavitation.

Albumins↗
PubMed1997

The influence of contrast agents on hemorrhage produced by lithotripter fields.

Ultrasonic contrast agents greatly increase the side effects of low-amplitude lithotripter fields in mice. Using a piezoelectric lithotripter, adult mice were exposed to 200 lithotripter pulses with a peak positive pressure amplitude of 2 MPa. During the exposure period, mice were injected with approximately 0.1 mL of the ultrasonic contrast agent Albunex. For comparison, another group of mice experienced the same lithotripter exposures, but were not injected with contrast agent. Following exposures, animals were sacrificed and observed for hemorrhage in various organs and tissues. Mice exposed to the lithotripter field alone had minimal hemorrhage only in the intestine and lung. In comparison, mice injected with Albunex during exposure exhibited extensive hemorrhage in the intestine, kidney, muscle, mesentery, stomach, bladder, seminal vesicle and fat.

Albumins↗
PubMed1997

Ultrasound enhancement of rabbit femoral artery thrombolysis.

Experiments were conducted to evaluate the potential of low-intensity, externally applied ultrasound to accelerate arterial thrombolysis in an animal model and to characterize potential effects of ultrasound exposure on vessel wall morphology. The femoral arteries of 32 rabbits were exposed, a flowprobe was positioned around the vessel, and a stenosis produced with two circumferential silk sutures to reduce flow by 50%. Thrombosis was achieved by injecting thrombin through the cannulated superficial epigastric branch into a 1-cm segment of femoral artery which was isolated for 20 min. Streptokinase was administered intravenously as a 15,000 U/kg bolus followed by an infusion of 15,000 U/kg per h. Ultrasound (1 MHz, 2 W/cm2) was delivered to the thrombosed vessel during streptokinase administration in 17 animals, and 15 control animals received sham ultrasound only. Thrombolysis occurred in nine of 17 (53%) animals receiving both streptokinase and ultrasound, and this was significantly greater than the rate in animals receiving streptokinase alone (2/15, 13%; P=0.025). Ultrasound caused a mean temperature elevation of 4 degrees C in exposed tissues. Light and electron microscopy demonstrated increased platelet accumulation on thrombi in ultrasound-treated vessels compared with controls. Endothelial cell vacuolation was seen by electron microscopy in ultrasound-exposed vessels. The results indicate that externally applied, low-intensity ultrasound can significantly enhance thrombolysis in a rabbit arterial model. Possible adverse effects are minor and include platelet accumulation, temperature elevation and minor endothelial changes. Externally applied ultrasound has potential value as an adjunct to thrombolytic therapy.

Animals↗
PubMed1996

Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "re-presentation" of exogenous antigen by tumor-infiltrating antigen-presenting cells.

We show that interleukin 3 (IL-3) enhances the generation of tumor-specific cytotoxic T lymphocytes (CTLs) through the stimulation of host antigen-presenting cells (APCs). The BALB/c (H-2d) spontaneous lung carcinoma line 1 was modified by gene transfection to express ovalbumin as a nominal "tumor antigen" and to secrete IL-3, a cytokine enhancing myeloid development. IL-3-transfected tumor cells are less tumorigenic than the parental cell line, and tumor-infiltrating lymphocytes isolated from these tumors contain increased numbers of tumor-specific CTLs. By using B3Z86/90.14 (B3Z), a unique T-cell hybridoma system restricted to ovalbumin/H-2b and implanting the tumors in (BALB/c x C57BL/6)F1 (H-2d/b) mice, we demonstrate that the IL-3-transfected tumors contain an increased number of a rare population of host cells that can process and "re-present" tumor antigen to CTLs. Electron microscopy allowed direct visualization of these host APCs, and these studies, along with surface marker phenotyping, indicate that these APCs are macrophage-like. The identification of these cells and their enhancement by IL-3 offers a new opportunity for tumor immunotherapy.

Animals↗
PubMed1996

Thresholds for ultrasonically induced lung hemorrhage in neonatal swine.

The threshold for generation of lung hemorrhage in adult mice by pulsed ultrasound has been shown to be approximately 1 MPa at the surface of the lung (10-microseconds pulse and a carrier frequency of 2 MHz). This investigation used neonatal swine to determine if the findings for mice can be generalized to other species. After exploratory observations, the inverse sampling method was used in a primary study (22 animals, 88 exposure sites) to determine the threshold for lung hemorrhage in neonatal swine. The primary study was followed by a separate confirmation study (13 animals, 48 exposure sites), testing the conclusions of the first study and comparing damage at subthreshold levels with sham-exposed animals. A separate investigation explored the histological nature of tissue damage at suprathreshold levels. A 2.3-MHz focused transducer (10 microseconds at 100-Hz pulse-repetition frequency) was incremented vertically for a distance of 2 cm over the chest of the subject for a total exposure period of 16 min. Animals were euthanized and lungs were scored by visual inspection for numbers and areas of gross hemorrhages. The threshold level for hemorrhage was approximately 1.5 MPa peak positive pressure in water at the surface of the animal or, at the surface of the lung, 1.1 MPa peak positive pressure, 1 MPa fundamental pressure, 0.9 MPa maximum negative pressure, 25 W cm-2 pulse average intensity or a mechanical index of 0.6. These values are essentially the same as those reported for adult mice.

Animals↗
PubMed1996

Bioeffects of positive and negative acoustic pressures in vivo.

In water, the inertial collapse of a bubble is more violent after expansion by a negative acoustic pressure pulse than when directly compressed by a positive pulse of equal amplitude and duration. In tissues, gas bodies may be limited in their ability to expand and, therefore, the relatively strong effectiveness of negative pressure excursions may be tempered. To determine the relative effectiveness of positive and negative pressure pulses in vivo, the mortality rate of Drosophila larvae was determined as a function of exposure to microsecond length, nearly unipolar, positive and negative pressure pulses. Air-filled tracheae in the larvae serve as biological models of small, constrained bubbles. Death from exposure to ultrasound has previously been correlated with the presence of air in the respiratory system. The degree of hemorrhage in murine lung was also compared using positive and negative pulses. The high sensitivity of lung to exposure to ultrasound also depends on its gas content. The mammalian lung is much more complex than the respiratory system of insect larvae and, at the present time, it is not clear that acoustic cavitation is the physical mechanism for hemorrhage. A spark from an electrohydraulic lithotripter was used to produce a spherically diverging positive pulse. An isolated negative pulse was generated by reflection of the lithotripter pulse from a pressure release interface. Pulse amplitudes ranging from 1 to 5 MPa were obtained by changing the proximity of the source to the biological target. For both biological effects, the positive pulse was found to be at least as damaging as the negative pulse at comparable temporal peak pressure levels. These observations may be relevant to an evaluation of the mechanical index (MI) as an exposure parameter for tissues including lung since MI currently is defined in terms of the magnitude of the negative pressure in the ultrasound field.

Acoustics↗
PubMed1995

In vitro radiation sensitivity of mouse lung fibroblasts isolated by flow cytometry.

PURPOSE: Recently, we have isolated two major fibroblast cells (Thy-1+, Thy-1-) from mouse LAF1 lung tissue using the anti-Thy-1 antibody expression and fluorescence activated cell sorter. To examine the possibility that x- or gamma-ray-induced pulmonary fibrosis at the late stage of injury could arise from radioresistant cell subpopulations, the radiation sensitivities of Thy-1+ and Thy-1- cells were evaluated by the colony forming assay. METHODS AND MATERIALS: Cell survival curves, repair of potentially lethal damage (PLD) and sublethal damage (SLD), and cell-age response curves were obtained after Cs-137 gamma-ray irradiation. RESULTS: The cell survival curves measured after 0-10 Gy gamma-ray showed that Thy-1+ cells were slightly more radioresistant than Thy-1- cells. The D0, n, alpha, and beta values measured from the survival curves also confirmed this observation. After a single dose of 10 Gy, a small amount of PLD repair was observed in Thy-1- cells, while no PLD repair was found in Thy-1+ cells. Although the initial cell survival level of Thy-1- cells was lower, the final survival levels of Thy-1+ and Thy-1- cells became identical at 8 h after irradiation due to the PLD repair. After split-dose irradiation of 4 Gy followed by 4 Gy, a similar extent and rate of SLD repair was found in Thy-1+ and Thy-1- cells. Cell-age response curves were obtained from irradiated G0/G1, S, and G2M cells separated by centrifugal elutriation and irradiated with 8 Gy gamma-ray. The results indicated that Thy-1+ and Thy-1- cells had a similar S resistant, and G1, G2M-sensitive radiation cell-age response curve. CONCLUSIONS: This study suggests that the selection of radioresistant lung fibroblast may not be responsible for the development of lung fibrosis in irradiated LAF1 mouse.

Animals↗
PubMed1994

Acceleration of fibrinolysis by ultrasound in a rabbit ear model of small vessel injury.

High frequency ultrasound has been previously shown to accelerate fibrinolysis in vitro at intensities that are potentially applicable for noninvasive administration clinically. To extend these findings in vivo, we have investigated the effects of ultrasound on fibrinolysis induced by streptokinase in a rabbit model of small vessel injury. Full thickness puncture wounds were made in rabbit ears with a scalpel blade. The rabbits were rested for 2-3 hours after cessation of bleeding to allow maturation of hemostatic plugs. Saline or streptokinase was then infused intravenously, and ultrasound was applied to some lesions at 1 MHz with a 50% duty cycle at 1 W/cm2 net intensity. Ear lesions in rabbits treated with saline showed no bleeding after 30 minutes whether they were exposed to ultrasound or not. Streptokinase alone induced bleeding after 19.7 +/- 5.5 minutes. Application of ultrasound significantly reduced the time to bleeding in streptokinase treated rabbits to 7.5 +/- 3.9 minutes (p < .002). The times to bleeding with "sham" ultrasound (18.8 +/- 5.6 minutes) and heating of the ear (18.0 +/- 5.6 minutes) during streptokinase administration were not significantly different compared to streptokinase alone. Histologic examination revealed that application of ultrasound resulted in a mild increase in interstitial edema and accumulation of polymorphonuclear leukocytes but did not cause vascular or other tissue damage. We conclude that the noninvasive, percutaneous application of ultrasound significantly accelerated streptokinase-induced fibrinolysis in this rabbit model of small vessel injury.

Analysis of Variance↗
PubMed1994

Morphological correlates of fractionated radiation of the mouse lung: early and late effects.

PURPOSE: The definition and quantitation of radiation-induced morphologic alterations in murine lungs is presented. METHODS AND MATERIALS: The extent of injury to the lung, which is the dose-limiting organ in the thorax, may be reduced by fractionating the total radiation exposure to permit partial repair of radiation-induced damage between fraction administration and also to permit a larger total exposure to be administered. We previously reported that, following fractionated radiation exposures, as the dose/fraction decreases, the total dose to reach an isoeffect increases, with an alpha/beta ratio of 3.2 and 3.0 for breathing rates and lethality, respectively. In the present report, we provide comparative morphologic evaluation of the effects of weekly fractionated (three doses at one dose/week), daily fractionated (15 doses at 1/diem), and hyperfractionated (30 doses at 2/diem) radiation exposures. The doses administered within each group were uniform. To determine morphologic alterations, LAF1 mice were irradiated with 3, 15, and 30 fractions delivered in 19 days overall treatment time. In the hyperfractionation schedule, the two fractions per day were separated by a 6-h time interval. Total doses were as follows: 15-21 Gy for weekly fractionation, 30-41.5 Gy for daily fractionation, and 30-49.5 Gy for hyperfractionated schedules. Lung tissue, recovered either 24 or 72 weeks following the final exposure, was evaluated by transmission and scanning electron microscopy and light microscopy. RESULTS: Using a series of morphologic parameters, a total dose of 15 Gy in the weekly treatment schedule was found to be equivalent to a total dose of 30 Gy in the daily fractionation schedule and 37 Gy in the hyperfractionated treatment regimen at 24 weeks postirradiation. Measured at 72 weeks postirradiation, total exposures of 15 Gy on the weekly fractionation regimen corresponded to total exposures of approximately 30 Gy in both the daily fractionated and hyperfractionated regimens. Morphological damage was not uniform throughout the exposed lung and tended to be concentrated in lobes or portions of lobes. CONCLUSIONS: In the three fractionation regimens studied, there is progressive sparing of the lung with increased fractionation (i.e., weekly < daily < twice daily) during the pneumonitic stage (24 weeks postirradiation). Both daily and twice daily fractionations provide increased sparing over weekly fractionation during the fibrotic stages (72 weeks postirradiation), but were not markedly different from each other (i.e., weekly < daily = twice daily).

Animals↗
PubMed1993

Pulmonary changes induced by combined mouse beta-interferon (rMuIFN-beta) and irradiation in normal mice--toxic versus protective effects.

This study in normal mice was undertaken to investigate possible enhancement of pulmonary toxicity by interferon-beta (IFN-beta) combined with single doses of irradiation. A pharmacokinetic study preceded the toxicity study to determine the optimal route and timing of IFN administration. Graded single doses of radiation were combined with graded doses of IFN. Pulmonary toxicity was determined using endpoints of alveolar surfactant and procollagen in lung lavage fluid at 7 days, breathing frequency, lethality and histology. Increased lethality was seen when IFN was combined with irradiation at 12.5 Gy vs. irradiation alone. This occurred between 20 and 30 weeks post treatment with no increased breathing frequency or surfactant release, suggesting independent mechanisms of injury. Increased breathing frequency after 40 weeks, usually associated with fibrosis, was less pronounced for IFN treated vs. irradiation only controls. Ultrastructural studies at 72 weeks suggest reduced fibrosis in lungs of IFN treated vs. irradiation only controls. Supporting this was the finding that Procollagen III, a biosynthetic precursor of collagen, was increased in the lavage fluid at 7 days for all radiation doses but decreased with the addition of IFN at 12.5 and 15 Gy. Interferons can act either as sensitizers or radioprotectors, depending on the biological system and type of interferon. Our study suggests that while IFN-beta may increase the acute effects of radiation in the mouse lung, some protection from radiation-induced fibrosis, possibly related to alteration of immune mechanisms, may exist.

Animals↗
PubMed1993

Morphological effects of pulsed ultrasound in the lung.

We have previously described the induction of subcapsular hemorrhage in the murine lung by extracorporeal shock wave lithotripsy at exposures of 2 MPa (Hartman et al. 1990) and pulsed ultrasound (Child et al. 1990). Since extravasation of erythrocytes and alveolar flooding are prominent, we proposed to determine whether or not the injury was progressive, by continuing to develop following termination of exposure, and by localizing where the injury was developing. Mice were exposed to 10 microsecond impulses at 1.6 MPa for 3 min and sacrificed either immediately or 5 min following exposure. When observed with both light and transmission electron microscopy, there was no gradation in lung injury, with a sharp demarcation of the hemorrhagic area. Moreover, both type I pneumocytes and capillary endothelial cells were injured, causing direct continuities between vessel lumina and alveolar spaces. In the absence of extravasation, the tissue appeared normal. There was no evidence that injury increased in severity during the first 5 min after exposure.

Animals↗
PubMed1992

Morphologic and functional characteristics of subpopulations of murine lung fibroblasts grown in vitro.

Fibrotic development is a common response of the lung to toxic or deleterious insult. For example, the lung is the dose-limiting organ for irradiation of the thorax for primary or metastatic lesions, due in large part to latent fibrosis. The development of the fibrotic response reflects a cascade of cell-cell and cell-extracellular matrix interactions, the ultimate target of which is the fibroblast. There is increasing evidence of subpopulations of pulmonary fibroblasts, which may have differing roles in either the initiation or progression of fibrosis. Recently we described two fibroblast subpopulations from the murine lung, which differ in the presence or absence of the membrane antigen Thy-1 (Phipps et al., 1989). These Thy-1+ and Thy-1- subpopulations are stable and differ in certain functions, such as the production of cytokines and the display of Class II MHC antigens. To determine the morphologic development of the two subpopulations and their growth characteristics in vitro, cultures of the two cell subtypes were prepared for transmission and scanning electron microscopy at varying stages of growth. Thy-1+ fibroblasts are more spindle-shaped, contain intracellular lipid, exhibit abundant cell-cell contacts, and are capable of secreting large amounts of collagen and modest amounts of fibronectin. Thy-1- fibroblasts are more rounded and spread, contain no intracellular lipid droplets, possess more intracellular microfilaments and microtubules, and synthesize less collagen and more fibronectin than do Thy-1+ cells. There are no significant differences between the two subpopulations insofar as growth rates are concerned, but Thy-1+ fibroblasts possess an additional DNA peak during periods of early growth.

Animals↗
PubMed1992

Ultrasonic heating of lung tissue.

Tests with mice show that lung tissue is not selectively heated in comparison with other soft tissues and that lung has an efficient mechanism for dissipating that heat which is produced. Temperatures measured with a fine thermocouple placed at the outer surface of the mouse lung show approximately 1 degree C total rise in temperature in the living animal for an incident intensity of 1 W/cm2 (4 MHz, unfocused sound field).

Animals↗
PubMed1992

Cat tracheal gland cells in primary culture.

Conditions for the primary culture of isolated cat tracheal gland cells were established. Cells plated onto glutaraldehyde-fixed gels of rat tail collagen grew to confluency after 8 days of culture forming a monolayer of cuboidal cells with ultrastructural characteristics of epithelial cells and immunoreactivity to antikeratins. Cultured cells synthesized and released radiolabeled high-molecular-weight glycoconjugates. Glycoconjugate secretion was increased approximately 10% in response to the cholinergic agonist, carbachol. Secretion of glycoconjugates was unrelated to regulated exocrine secretion, since these cells were devoid of secretion granules as assessed by light and electron microscopy. Confluent cultures also generated a spontaneous potential difference and short-circuit current, which were both inhibited by ouabain and increased by carbachol. This suggested gland cells contribute to fluid secretion by active ion-transport mechanisms. We also plated cells onto unfixed collagen gels that were released from the culture dish at confluency. Cells were columnar with apically oriented secretion granules that stained with alcian blue and for blood group A immunoreactivity. Secretion of radiolabeled high-molecular-weight glycoconjugates was increased 27% by carbachol. These cell culture systems may serve as models to investigate glandular secretory mechanisms and their regulation.

Animals↗
PubMed1992

Differential collagen and fibronectin production by Thy 1+ and Thy 1- lung fibroblast subpopulations.

Pulmonary fibrosis resulting from diverse etiologies is characterized by proliferation of fibroblasts and excessive accumulation of interstitial collagen. Whether fibrosis is associated with selective expansion of fibroblast subpopulations differing in amounts or types of collagens synthesized is unknown. We have previously isolated lines and clones of normal murine lung fibroblasts based on the presence of the Thy 1 surface antigen. These subpopulations differ in morphology, growth characteristics, and display of class II major histocompatibility complex antigens (R.P. Phipps, D.P. Penney, P. Keng, H. Quill, A. Paxhia, S. Derdak, and M. E. Felch. Am. J. Respir. Cell Mol. Biol. 1: 65-74, 1989). We evaluated the amounts and types of collagen and fibronectin synthesized by Thy 1+ (Fib2-T-3+) and Thy 1- (Fib2-T-4-) lung fibroblast lines and clones. Thy 1+ fibroblast line synthesized two- to threefold more collagen and noncollagen protein than the Thy 1- line. In contrast, both the Thy 1+ and Thy 1- lines synthesized similar amounts of fibronectin. Thy 1+ and Thy 1- lines and clones expressed mRNA for alpha 1(I)-and alpha 1(III)-procollagen and synthesized both types (predominantly type I and lesser amounts of type III) of collagen, protein, and mRNA. The fibroblast clones varied significantly in total collagen and fibronectin production, with one Thy 1- clone (D3) synthesizing the largest amount of collagen but relatively little fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗