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Biomedical subjects

J E Artwohl

Publications and source records attributed to J E Artwohl.

At least 19 recordsLinked to original sources
PubMed2000

Physiologic and behavioral assessment of rabbits immunized with Freund's complete adjuvant.

Although the use of Freund's Complete Adjuvant (FCA) has been discouraged for the production of polyclonal antibodies, little clinical evidence supports the belief that FCA necessarily affects the well-being of immunized rabbits. We designed the present study to determine whether immunization at multiple sites with small volumes of Freund's adjuvant affects rabbit well-being. We injected 18 female New Zealand White rabbits (six animals per group) with antigen in FCA, Freund's Incomplete Adjuvant, or physiologic saline in the following volumes and routes: 0.02 to 0.03 mL intradermally in each of 30 to 40 sites and 0.1 mL subcutaneously in each of two sites. The body weight, temperature, complete blood count, and behavior of the rabbits in the home cage, upon handling, and in an open field did not differ significantly among the immunization groups during the 7-week assessment period. Only the degree of induration around injection sites differed: as expected, FCA induced the greatest response at the injection sites, but the sites were neither ulcerative nor necrotic, nor did palpation of the sites induce any apparent discomfort to the rabbits. We conclude that FCA may be used safely and humanely in rabbits if small volumes are injected intradermally or subcutaneously in multiple sites.

Animal Welfare↗
PubMed2000

Outbreak of Pasteurella pneumotropica in a closed colony of STOCK-Cd28(tm1Mak) mice.

Fifteen mice with Pasteurella pneumotropica orbital abscesses were noted in mice that were homozygous for a targeted Cd28 gene mutation. Only one mouse heterozygous for the Cd28 mutation was affected. According to phenotypic reactions and 16S rDNA sequencing, the isolates were most similar to biotype Heyl. This article provides evidence for an immunologic basis of susceptibility to P. pneumotropica infection. Fifteen mice with Pasteurella pneumotropica orbital abscesses were noted in mice that were homozygous for a targeted Cd28 gene mutation. Only one mouse heterozygous for the Cd28 mutation was affected. According to phenotypic reactions and 16S rDNA sequencing, the isolates were most similar to biotype Heyl. This article provides evidence for an immunologic basis of susceptibility to P. pneumotropica infection.

Animals↗
PubMed2000

Verification of bacterial killing effects of cage wash time and temperature combinations using standard penicylinder methods.

We conducted the present study to evaluate various time and hot-water temperature combinations necessary to kill three common bacterial species in standardized cultures on stainless steel penicylinders, in accordance with methods approved by the Association of Official Analytical Chemists. Exposure for no more than 2 sec to water at 82.2 degrees C killed all three bacterial species, as did exposure for 3 sec to water at 80 degrees C, 4 sec at 77.8 degrees C, and 5 sec at 75.6 degrees C. We conclude that temperatures in the range of 75.6 degrees C to 82.2 degrees C will effectively kill vegetative bacteria in a matter of seconds and that failure to kill these bacteria in cagewash operations, with belt travel times in minutes rather than seconds, is due to other factors that prevent the effective application of sufficiently hot water to the bacterial load.

Animals↗
PubMed1998

Endothelin-1-like immunoreactivity in a new rodent model of spontaneous hypertension.

The purpose of this study was to determine plasma and tissue endothelin-1 (ET-1)-like immunoreactivity in a new rodent model of spontaneous hypertension. Plasma and tissues were procured from pentobarbital-anesthetized 16- to 18-week-old male hamsters with spontaneous hypertension and genetically/age-matched normotensive hamsters. We found that ET-1-like immunoreactivity in the plasma was similar in both groups. However, renal and cardiac ET-1-like immunoreactivity was 11- and 1.7-fold higher in spontaneously hypertensive hamsters relative to normotensive hamsters, respectively (P < .05). ET-1-like immunoreactivity was slightly, but significantly, lower in the lung and spleen of spontaneously hypertensive hamsters relative to normotensive hamsters (P < .05). ET-1-like immunoreactivity in the liver and brain was similar in both groups. We conclude that ET-1-like immunoreactivity is significantly higher in two target organs for hypertension, kidney and heart, but not in plasma or brain of adult male hamsters with spontaneous hypertension, relative to genetically/age-matched normotensive hamsters. We suggest that renal and cardiac ET-1 could play a role in the natural history of spontaneous hypertension in hamsters.

Animals↗
PubMed1997

Suppression of apoptosis by bcl-2 does not prevent p53-mediated control of experimental metastasis and anchorage dependence.

Mutations in the p53 tumor suppressor gene are frequently associated with the metastatic stage of tumor progression. Inactivation of p53 was shown to promote metastasis under experimental conditions. To determine the p53 functions that are involved in the control of tumor metastasis, we compared properties of three types of transformed mouse fibroblasts: with intact p53, with p53-mediated apoptosis suppressed by bcl-2 and with p53 inactivated by dominant negative mutants. Although expression of bcl-2 blocked apoptosis in detached cells and increased tumor cell survival in the blood circulation, it was insufficient to affect the ability of p53 to cause cell cycle arrest in detached cells and suppress experimental metastasis. For the suppression of metastasis complete inactivation of p53 was required. We conclude that the apoptotic function of p53 is dispensable for the p53-dependent suppression of experimental metastasis that is presumably achieved by controlling anchorage dependence. These data provide a possible explanation to dramatic differences in values of bcl-2 and mutant p53 as prognostic markers in human cancer.

Animals↗
PubMed1997

Initial characterization of hamsters with spontaneous hypertension.

The purpose of this study was to begin to characterize a new inbred strain of adult male hamsters with established spontaneous hypertension along with their genetically/age-matched normotensive controls. We found that mean arterial pressure was 162+/-3 mm Hg in hypertensive hamsters and 94+/-4 mm Hg in controls (mean+/-SEM; P<.05). Body weight was significantly lower in hypertensive hamsters relative to normotensive hamsters (P<.05). Hypertension was associated with a significant increase in heart weight, thickness of the left ventricular wall, and amplitude of the QRS complex in standard electrocardiographic leads I and aVR (P<.05). No gross or microscopic abnormalities were observed in other organs. Plasma renin activity and the number of circulating neutrophils were significantly increased in hypertensive hamsters relative to controls (P<.05). Serum concentrations of creatinine, blood urea nitrogen, sodium, potassium, and calcium as well as urinalysis were similar in both groups. Overall, these data suggest that the spontaneously hypertensive hamster could be a suitable model for the study of spontaneous hypertension.

Animals↗
PubMed1996

Swollen eyelid associated with Foleyella sp infection in a chameleon.

An adult female Oustalet's chameleon was examined to determine the cause of a fluctuant enlargement of the right superior eyelid. Surgical exploration of the subcutaneous tissues of the eyelid revealed live microfilarial parasites, which were identified later as Foleyella sp. These parasites, although seldomly reported, are fairly common in imported chameleons and can be detected during examination of blood smears. Surgical removal continues to be the treatment of choice for these parasites, because the efficacy and safety of many new anthelmintic agents have not been determined for use in chameleons.

Animals↗
PubMed1995

Comparisons of radioiodoestradiol blood-tissue exchange after intravenous or intraarterial injection.

PURPOSE: Our study determines and compares how the major organs of large animals handle exogenous halogenated bioactive sex steroids within the first minutes after their i.v. or i.a. injection. The rationale is that an understanding is needed of the acute physiological events because they affect decisions for how to optimize delivery of radiohalogenated sex steroid receptor ligands for purposes of medical imaging and modes of radiotherapy. METHODS AND MATERIALS: We used an indicator dilution technique that allows monitoring of blood-tissue exchange of radioactivity in a continuous manner in anesthetized surgically prepared swine. RESULTS: In swine, with by-passed liver circulation, the lungs allow the vast majority of [I-125]-16 alpha-iodo-17 beta-estradiol ([I-125]E) to be extracted from the blood perfusing the lung in the initial transit after i.v. injection in vivo. Similar outcome was observed for most major organs, including the CNS, intestines, spleen, peripheral appendages, and kidneys after i.a. injection of [I-125]E in vivo. However, within minutes the organs released the [I-125]E in its original chemical form back into the vascular system, with the exception of estrogen receptor (ER) rich tissues and the kidneys that retained the [I-125]E in its original form, although in the kidneys a nonpolar metabolite also accumulated. CONCLUSION: Our experiments confirm in a large animal model that radioiodoestradiol can be sequestered or concentrated in ER-rich sites. The liver and sex steroid receptor-rich organs modify considerably, by metabolism and sequestration, respectively, the acute distribution of bioactive steroids. Our data indicate potential for detection of ER in vivo in hormone-sensitive tumors, that is, in breast and endometrial cancers, and offer improved understanding of the recent studies in subjects with breast cancer that demonstrated that receptor imaging in vivo of steroid receptors with high-affinity radiolabeled ligands is possible in a clinical setting.

Animals↗
PubMed1993

A comparison of euthanasia methods in rats, using carbon dioxide in prefilled and fixed flow rate filled chambers.

The two methods (prefilled and fixed flow rate filled chambers) recommended in the 1993 AVMA Euthanasia Panel report for using carbon dioxide to euthanatize rats were evaluated in terms of their effect on behavior and selected blood gas values. Responses were videotaped during exposure to > or = 90% carbon dioxide in a prefilled chamber or a gradually filled chamber, using a fixed flow rate of 20% chamber volume/min. Arterial blood samples were taken to determine partial pressure of oxygen, partial pressure of carbon dioxide, pH, and oxygen saturation prior to entering the chamber and at time points determined by rats' responses to carbon dioxide. Rats showed similar reactions when exposed to carbon dioxide by either method. Significant differences in mean time for each response to occur were seen between euthanasia methods. Maintaining a near atmospheric oxygen chamber concentration by using a 75% CO2: 20% O2: 5% N2 gas mixture to gradually fill the chamber did not change rats' reactions upon exposure. Significant differences were found between pre-exposure values and values from samples obtained when rats became immobile after entering the prefilled chamber. Partial pressure of carbon dioxide significantly increased, and pH and percent oxygen saturation significantly decreased from pre-exposure values in all samples obtained after rats entered the gradually filled chamber. Partial pressure of oxygen in these rats was greater than or equal to pre-exposure levels in all samples. Rats appeared sedated because of the anesthetic effects of carbon dioxide when immobility was observed. Distress was not observed in the rats when either method of euthanasia was used.

Animals↗
PubMed1991

Biodistribution, with high uptake by the reproductive tract, of an intraperitoneally infused radiohalogenated steroidal estrogen-receptor ligand.

We infused [123I]16 alpha-(123I)-iodo-estradiol ([123I]E2) intraperitoneally (i.p.) into swine to study its biodistribution and to explore the i.p. use of radiohalogenated steroid estrogen-receptor (ER) ligands as a potential option for diagnosing and treating intra-abdominal, retroperitoneal, and distant sites of advanced ER-rich malignancies. Fifty to 80% of the radiolabel was absorbed from the peritoneal cavity within 30 minutes, and 30 to 50% of the infused radiolabel was excreted in the urine within 2 hr. The rate of biliary clearance was maximal within 25 minutes. At 3 hr, the ER-rich reproductive tract had greater than 63 times the concentration of radiolabel in blood; the former was blocked by non-labeled competitors for ER. Uptake by non-ER-rich tissues, compared to blood, ranged from 0.7:1 (heart and lungs) to 16:1 (spleen); the omentum, however, exhibited a concentration as high as 64:1, which was not blocked by non-labeled ER ligands. Uptake by ER-rich target tissue remained high when charcoal was used to prevent reabsorption of radiolabel from the digestive tract after its biliary excretion, and when the products of biliary excretion were removed by catheterization of the common bile duct. Neither charcoal nor exteriorization of bile appeared to affect urinary clearance of the radiolabel over the time course of the experiments. Taken together with the recent development of syntheses that yield radiohalogenated sex steroid receptor ligands of high specific activity, our findings are encouraging for the potential application of radiolabeled ligands as i.p. administered pharmaceuticals. The advantage of the i.p. route is that it provides direct uptake of the pharmaceutical by free-floating clusters and individual cancer cells in ascitic fluid, as well as delivery via the circulation to vascularized intra- and/or extraperitoneal metastases.

Abdomen↗
PubMed1991

Rapid liver metabolism, urinary and biliary excretion, and enterohepatic circulation of 16 alpha-radioiodo-17 beta-estradiol.

The radiohalogenated estrogen 16 alpha-[123I]iodo-17 beta-estradiol ([123I]E2) is emerging as a diagnostic tool for imaging of ER-rich malignant tumors, with potential application for site-directed radiotherapy. Clinical use requires an accurate accounting for the biodistribution of the radioactivity, including an assessment of its enterohepatic circulation. We investigated the metabolism and circulation of [125I]E2 in the enterohepatic system in swine, a pharmacokinetic model that resembles humans. With indicator dilution methods, we found that, after its injection into the portal vein, more than 99% of [125I]E2 was cleared from the blood by the liver during the first pass. Water-soluble metabolites were then partly released into the blood and partly excreted into bile. After injection of [125I]E2 into the external jugular vein, one-third of the radioactivity was excreted in bile and two-thirds in the urine. More than 90% of the radioactivity in urine and bile was that of [125I]E2-glucuronide or [125I]E2-sulfate; only a very small fraction of the excreted radioactivity was from free 125I. Radioactivity in bile collected from one swine after i.v. injection of [125I]E2, and then infused into the proximal duodenum of a second swine, was almost totally absorbed during passage through the intestine at 5-7 hr after infusion. The reabsorbed radioactivity was cleared in the urine.

Animals↗