Particle-stabilized bubbles for enhanced organ ultrasound imaging.
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Animals↗
Biomedical subjects
R B Baggs
Publications and source records attributed to R B Baggs.
Immune modulation in the guinea pig using cortisone acetate.
Cortisone acetate was administered to a group of guinea pigs (Cavia porcellus) at 0 (control), 20 (low) or 200 (high) mg/kg. Steroid was given daily for two individual 7 day periods, separated by 7 days of no treatment. The effects of this steroid on body weight gain, thymic weight, total and differential leukocyte counts, serum antibody titer against a bacterin, dermal hypersensitivity response to a sensitizing agent and histological evaluation of lymphoid and other tissues were evaluated. Significant differences in body weight gain (p less than 0.05) and thymic weight (p less than .01) were noted. For total leukocyte count, no significant difference among treatment groups at individual time points was noted (p greater than .10), while significant differences were seen in lymphocyte and neutrophil counts (p less than .01). A significant difference in antibody titer among the treatment groups was observed (p less than .01). For the dermal hypersensitivity response, there was no consistent pattern among the treatment groups in gross (macroscopic) skin reactions. Microscopically, differences were seen in the inflammatory response among the treatment groups. Histologically, steroid related changes were seen in thymus, spleen, lymph node and liver. At necropsy, 24 of 40 animals had lesions of focal necrotizing hepatitis. Three affected animals died and remaining animals showed no clinical illness. The cause of the necrotizing hepatitis could not be determined by culture, special stains, electron microscopy, serology or by attempts at transmission with affected liver samples.
Animals↗
Experimental bone and bone marrow metastasis in laboratory animals.
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Animals↗
Lymphocytic infiltration and cytotoxicity under hypoxic conditions in the EMT6 mouse mammary tumor.
Infiltration of lymphocytes, neutrophils and macrophages was evaluated in hypoxic and well-oxygenated areas of the EMT6 mouse mammary adenocarcinoma, by in vivo staining with the fluorescent dye Hoechst 33342 followed by cell sorting on the basis of fluorescence intensity. Tumors were grouped by days post-injection (days 11-14, 15-17 and 20-27). As lymphocytes are the only host cell population in this tumor model to possess lytic activity against EMT6 tumor cells, the ability of sensitized T lymphocytes to lyse syngeneic EMT6 cells was examined under conditions of varying oxygen concentrations. Infiltrating lymphocytes were detected to the same extent in cell fractions from both areas in all tumors. In contrast, neutrophils were found in significantly higher percentages in the hypoxic population than in the well-oxygenated cell fraction of all but the largest tumors. Macrophages were present in significantly higher percentages in the well-oxygenated fraction than in the hypoxic fraction of day-11 to -14 tumors. Extreme radiobiological hypoxia (0% O2) resulted in a significant decrease in T-cell-mediated lysis of EMT6 tumor cells, compared to lysis in room air (20% O2), but lysis was not impaired under conditions of mild radiobiological hypoxia (1% O2). Our study indicates that host-cell infiltration into areas of differing oxygenation may be quantitated via in situ Hoechst staining followed by cell sorting; in the EMT6 tumor, lymphocytes appear to infiltrate hypoxic areas to the same extent as well-oxygenated areas, and T-lymphocyte killing of syngeneic tumor cells is significantly reduced, although still present, under these hypoxic conditions.
Animals↗
Pathogenesis of vertebral metastasis and epidural spinal cord compression.
The authors have studied the sequential events in the process of vertebral metastasis that result in spinal cord compression. Different tumor cell lines were injected into the systemic arterial circulation of syngeneic or nude mice, and they were killed at timed intervals after injection or when they became paraplegic. The following observations were made. The tumor cells lodged and grew in the hematopoietic bone marrow of the vertebrae. Cancer cells in the vertebral marrow cavity invaded into the spinal canal through the foramina of the vertebral veins rather than destroying the cortical bone. Tumor cell lines that grew in an infiltrative fashion migrated toward a posterior location in the spinal canal, and compressed the spinal cord from a posterior direction. Tumor cell lines that grew as compact tumors formed a tumor mass at the same location from which the cells emerged from the vertebra, and compressed the cord predominantly from an anterior direction. Radiographic evidence of vertebral metastasis was a late event, and commonly associated with significant compression of the cord and extraosseous tumor. These experimental findings may help to establish better diagnostic and treatment strategies for patients with metastatic disease of the spine.
Animals↗
Central nervous system lesions in the Wistar rat fetus following direct fetal injections of cadmium.
During embryogenesis, maternal administration of cadmium (Cd) produces teratogenic effects, including hydrocephalus (HC), whereas later in gestation (during the fetal period), such effects have not been reported. Since there is little placental transfer of Cd late in gestation, such differences in response could be due to a lower Cd concentration in the fetus compared with the embryo after maternal Cd exposure, or could be due to a decreased sensitivity of the fetal central nervous system (CNS) to Cd. To test the susceptibility of the late gestational CNS to Cd, day 19 (sperm plug = day 0) rat fetuses were directly injected i.p. with CdCl2 (165, 100, 50 nmoles/fetus in 5 microliters saline). All fetuses in one horn were treated with Cd, while fetuses in the other horn were treated with saline. Fetuses were collected on day 21, grossly examined, weighed, fixed in Bouin's fixative, and later razor sectioned. Cd did not affect fetal viability or body weight. However, Cd caused a dose-dependent increase in hydrocephalus, with the total number of fetuses showing moderate to severe HC being 0/45, 0/11, 6/10, and 18/20 for controls, low, medium, and high doses, respectively. Mild HC was noted in one control and two low Cd fetuses. Brain necrosis was correlated with hydrocephalus, being observed in 0/45, 0/11, 5/10, and 16/20 fetuses, respectively. In medium-dose fetuses without HC or brain necrosis, extravasation of erythrocytes was noted histologically within the cortical parenchyma, suggesting that hemorrhaging may lead to brain necrosis and hydrocephalus in Cd-exposed fetuses. Thus, the fetal CNS is susceptible to the toxic effects of Cd.
Animals↗
Ultrasound contrast for hepatic tumors using IDE particles.
Iodipimide ethyl ester (IDE) can be formulated as dense spherical particles with narrow diameter distribution. When IDE particles are injected intravenously, the Kupffer cells of the hepatic sinusoids accumulate particles within 10 to 20 minutes, after which the clearance and excretion of IDE takes place. During the uptake phase, the dense particles act as scattering sites, increasing the echogenicity of normal liver tissue. In comparison, tumors and other lesions remain at pre-injection echogenicity, as they lack Kupffer cells and therefore do not retain particles. This report provides initial studies of contrast enhancement in rabbit livers with implanted VX2 tumors, scanned in vivo and evaluated ex vivo using pulse-echo techniques. The distribution of particles within hepatic lobules may explain why the observed echogenicity is greater than that predicted by single-particle backscatter theory. Directions for future improvements are discussed.
Animals↗
Use of Vicryl (polyglactin 910) mesh to limit epidural scar formation after laminectomy.
A variety of substances have been used at laminectomy sites to prevent postoperative epidural scarring. Free grafts of autologous subcutaneous fat are commonly used both clinically and experimentally. The free fat grafts usually survive, but decrease in size by about 50%. Postoperatively, subcutaneous seroma has been observed with the use of fat grafts, as well as recurrent symptoms of neural compression by the graft that required additional operations. When compared to the use of free grafts after laminectomy in dogs, Vicryl mesh produced slightly more scarring, but consistently less than that observed in control animals. The Vicryl mesh was resorbed by a minimal chronic inflammatory response over about 45 days. Seven of 11 fat-grafted zones showed signs of necrosis, at times with a greater collection of inflammatory cells than that associated with the Vicryl mesh. Of the 4 fat-grafted zones that showed good survival, 2 had gross evidence of neural compression. No surgical zone treated with Vicryl mesh exhibited evidence of neural compression. In view of these results, the use of Vicryl mesh at laminectomy sites may be a safer method of limiting postoperative epidural scar formation.
Animals↗
Immunization of cotton rats with the fusion (F) and large (G) glycoproteins of respiratory syncytial virus (RSV) protects against RSV challenge without potentiating RSV disease.
A formalin-inactivated respiratory syncytial virus (RSV) vaccine tested 22 years ago failed to protect infant vaccinees against RSV infection or disease. Instead, lower respiratory tract disease was enhanced during subsequent infection by RSV. Enhancement of pulmonary pathology is also observed when cotton rats are immunized with formalin-inactivated RSV and subsequently infected with this virus. A major question that must be addressed for each new paramyxovirus vaccine is whether the immunogen possesses the capacity to potentiate disease. In the present study, we evaluated a newly developed purified F and G glycoprotein vaccine over a wide dosage range for immunogenicity, efficacy and capacity to potentiate pulmonary pathology in cotton rats. In addition, a formalin-inactivated RSV vaccine, which served as a positive control for enhancement of pulmonary pathology, was evaluated simultaneously. The results of these comparisons indicate that the purified F and G glycoprotein vaccine was highly immunogenic and was efficacious even in animals that developed low levels of serum-neutralizing antibodies. Furthermore, the F and G vaccine did not induce potentiation of pulmonary pathology. In contrast, formalin-inactivated RSV potentiated RSV pulmonary histopathology, but there was a sparing of potentiation at high and low doses. Both the formalin-inactivated RSV and purified F and G preparations induced a high level of serum antibodies capable of binding to purified F and G glycoproteins but both sets of antibodies had significantly reduced neutralizing activity. These results are encouraging because they suggest that purified paramyxovirus glycoproteins might be used safely as a vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Reversible uranyl fluoride nephrotoxicity in the Long Evans rat.
Severity and duration of renal injury produced by low levels of uranyl fluoride (UO2F2) were examined in the rat. Rats received multiple ip injections of UO2F2 (cumulative dose: 0.66 or 1.32 mg U/kg body wt). Renal injury was characterized histologically by cellular and tubular necrosis of pars recta of proximal tubule (S2 and S3), with less severe cellular injury to thick ascending limb of loop of Henle and collecting tubule. Injury was evident when renal uranium levels were between 0.7 and 1.4 micrograms U/g wet kidney and was most severe when renal uranium burden was between 3.4 and 5.6 micrograms U/g. Repair of injury was rapid, with complete restoration within 35 days after exposure. Associated with injury were abnormalities in renal function, including impaired tubular reabsorption, proteinuria, and enzymuria, which appeared temporally related, to variable degrees, to progression of renal injury. Thus, reversible renal injury occurs in the rat at levels of uranium in kidney below the present Nuclear Regulatory Commission standard of 3 micrograms U/g kidney for renal injury in humans.
Animals↗
Liver glycogen and water storage: effect on ultrasound attenuation.
Glycogen has been shown in vitro to have a high specific absorption coefficient (ultrasound absorption in water per concentration) compared to other proteins. Depending on the amount of water which may accompany glycogen flux into and out of liver cells, the ultrasound attenuation coefficient of the liver may rise and fall with stored hepatic glycogen. This paper reports ex vivo studies on rats and in vivo studies on normal human volunteers before and after fasting. The results show a statistically significant difference in liver attenuation between well fed and fasted individuals. Generally, the attenuation difference is greater than 10%, and indicates that liver wet weight may not be strictly constant over glycogen storage cycles, as suggested in classic works. In contrast, no significant change in ultrasound backscatter is noted. The results point to the possible role of ultrasound attenuation measurements as a sensitive indicator of tissue physiology, and suggest that glycogen (feeding or fasting) must be controlled in tissue characterization experiments which compare liver attenuation coefficients of individuals and groups.
Animals↗
A murine model of experimental metastasis to bone and bone marrow.
Bone is a common site of metastasis in human cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal model. In this paper, we describe an animal model in which B16 melanoma cells injected in the left cardiac ventricle reproducibly colonize specific sites of the skeletal system of mice. Injection of 10(5) cells resulted in melanotic tumor colonies in most organs, including the skeletal system. Injection of 10(4) or fewer cells resulted in experimental metastasis almost entirely restricted to the skeletal system and ovary. In contrast, i.v. injection of 10(5) cells resulted in tumor colonies in the lung only. Left cardiac injection of 10(2) cells caused bone colonization, but the same number of cells injected i.v. did not colonize the lung. The number of bones with tumor colonies increased with increasing number of cells injected. Melanotic tumor colonies in the bone were characteristically distributed in the metaphysis of long bones and in the periphery of flat bones. Most animals developed paraplegia due to spinal cord compression by bony metastasis to the spine. Tumor colonization of bone occurred only in regions of bone containing hematopoietic bone marrow. This suggests that the injected tumor cells lodge, survive in the hematopoietic bone marrow environment, and grow to destroy adjacent bone. This experimental model of metastasis to bone will facilitate future studies of the pathophysiology and treatment of bone and bone marrow metastasis.
Animals↗
Myelin basic protein and magnetic resonance imaging for diagnosing radiation myelopathy.
The identification of radiation myelopathy using biochemical assays and imaging techniques has not previously been accomplished but has clear clinical application. Measurement of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) and visualization of the spinal cord using magnetic resonance imaging (MRI) gives a potentially accurate diagnosis of radiation myelopathy. Female New Zealand white rabbits were irradiated to the thoracic spinal cord with single doses of 15-45 Gy. Animals receiving higher doses (greater than or equal to 22 Gy) generally demonstrated an early paresis (4-8 weeks) that temporarily improved, and then progressed to complete paralysis by 14-18 weeks. MBP levels in the CSF became strikingly elevated to 100-1000 times the normal value. Subsequent, experiments in which rabbits were serially assessed for MBP levels demonstrated a transient elevation, which corresponded to the transient paresis, followed by dramatic elevations concurrent with the onset of paralysis. Magnetic resonance imaging (MRI) of the irradiated spinal cord showed a geographically distinct region of abnormality that corresponded to the radiation field. Histopathology demonstrated demyelination, focal astrocytosis, erythrodiapedesis, and perineuronal edema in the irradiated sections. It appears that MBP levels in the CSF reflect not only radiation-induced myelopathy but also transient demyelination, and that MRI may have the potential to indicate the region of damage.
Animals↗
Maternal toxicity and teratogenicity of tellurium dioxide in the Wistar rat: relationship to pair-feeding.
Tellurium dioxide (TeO2) induces hydrocephalus, edema, exophthalmia, ocular hemorrhage, umbilical hernia, undescended testes and small kidneys in day 20 Wistar rat fetuses when administered s.c. to pregnant dams from gestational day 15 to 19. At doses of 500 mumole/kg or greater, a 100% incidence of these findings and a reduction in maternal weight gain were observed. A pair-fed study at the dose of 500 mumole/kg of TeO2 was conducted to establish if the effects of tellurium were a result of a reduction in food intake or other maternal toxic responses. Two additional control groups of rats receiving tellurium or vehicle were fed ad libitum. After a comparable maternal weight gain from day 0 to 15, weight gain was significantly reduced in the treated groups and the pair-fed control. There was a reduction of fetal weight in the treated groups (p less than 0.01) and in the pair-fed control (p less than 0.02). There was a 100% incidence of the above anomalies in the litters of the two treated groups, but none in the pair-fed and control groups. No histological alterations other than a mild centrolobular fatty change in the liver were detected in the other organs from the tellurium exposed dams. Thus, tellurium induces both maternal toxicity and teratogenic effects in the rat where the teratogenicity is not mediated by alterations in the diet.
Abnormalities, Drug-Induced↗
The role of glycogen and phosphate in ultrasonic attenuation of liver.
The excess ultrasonic attenuation caused by adding glycogen and inorganic phosphate to liver homogenates has been studied to determine the underlying differences between attenuation coefficients of normal and diffusely diseased livers. Results show that glycogen has a higher than average specific absorption coefficient compared to other large molecular weight biomolecules. Since the glycogen content of liver can vary from 1%-10% of wet weight, this compound may have a major time-varying effect on the liver ultrasonic attenuation coefficient, even in normal subjects. In contrast, the excess attenuation of liver homogenate resulting from addition of inorganic phosphate was not significant at presumed physiological levels. The implications of these findings are discussed relative to tissue characterization efforts based on in vivo measurements of ultrasonic attenuation coefficients of liver.
Animals↗
Anesthetic-induced corneal lesions in developmentally sensitive rats.
Developmental critical periods for the induction of abnormalities by exposure to exogenous substances need not be confined to the early embryonic stage of organogenesis. The combination of ketamine hydrochloride and xylazine, two commonly used anesthetic agents, resulted in a corneal epithelial calcium deposition in 84% of rat pups whose exposure was limited to a single injection during the third postnatal week only. Concurrent exposure to ketamine hydrochloride, xylazine, and yohimbine, an alpha 2 adrenergic receptor antagonist, resulted in corneal lesions in only 6% of rat pups so exposed. The etiology is presently not understood but may involve interference with neurally directed corneal development. Corneal desiccation may also play a role. Altered drug metabolism, and toxic interactions resulting from a changing oxygen or light milieu are less likely etiologic mechanisms. Aspects of corneal development and mechanisms by which drugs can interact with and disturb normal maturational sequences can now be approached.
Anesthetics↗
Changes in hamster hepatic cytochrome P-450, ethoxycoumarin O-deethylase, and reduced NAD(P): menadione oxidoreductase following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Partial dissociation of temporal and dose-response relationships from elicited toxicity.
The temporal and dose-related characteristics of hepatic enzymes induced in the hamster by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were examined. Male Syrian golden hamsters received a single intraperitoneal injection of TCDD at a dose of 0-500 micrograms/kg. At various times up to 35 days, a number of variables were determined and compared: whole body, liver, and thymus weights; hepatic concentrations of cytochrome P-450 (P-450); and activities of 7-ethoxycoumarin O-deethylase (ECOD) and reduced NAD(P): menadione oxidoreductase (NMOR). Increased liver weights and decreased thymus weights were observed to be dose related. At day 7 following treatment, the approximate ED50 values for these responses were 15 and 100 micrograms/kg respectively. The ED50 values for the increase in hepatic P-450 concentrations and activities of ECOD and NMOR ranged from 0.5 to 2.0 micrograms/kg. At 10 and 500 micrograms/kg, NMOR activity remained maximally induced for up to 35 days. This was also the case for P-450 and ECOD activity at a dose of 10 micrograms/kg. At 500 micrograms/kg, both P-450 and ECOD demonstrated an induction up to day 4 followed by a decrease to near control levels by day 14. This decrease appeared to correlate with changes in hepatic morphology. These results demonstrate a dissociation of the induction of these hepatic enzymes from TCDD-induced lethality, in this species.
7-Alkoxycoumarin O-Dealkylase↗
Operant behavior in transition reflects neonatal exposure to cadmium.
Male Long-Evans rats were injected with 0, 1, 3, or 6 mg/kg of cadmium chloride on the first day of life. Animals free of morphological stigmata at weaning were selected for study. Tissue concentrations of cadmium and operant behavior under various fixed-ratio (FR) schedules of reinforcement were evaluated when these rats were adults. Dose-related increases in cadmium were present in the brains, livers, and kidneys. Dose-related differences in behavior were most evident during the transition from fixed ratio 25 (FR 25 or 25 responses/reinforcer) to FR 75. An inverted U describes the relationship between response output during the transition to FR 75 and cadmium chloride dose response output increased at 3 mg/kg and decreased at 6 mg/kg. The rate decreases were not correlated with weight loss that appeared after some of the animals exposed to 6 mg/kg reached 60 days of age. Challenge doses of d-amphetamine revealed no interaction between neonatal exposure to cadmium and d-amphetamine. The occurrence of alterations in operant behavior in animals that appeared normal on a number of preweaning evaluations suggests that operant behavior in transition was sensitive to subtle effects not observed with other commonly used tests. The data provide evidence for delayed effects in the adult that are due to neonatal exposure to cadmium.
Animals↗