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Biomedical subjects

F E Johnson

Publications and source records attributed to F E Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1989

Selective right-lung ventilation during emergency department thoracotomy.

Surgeons are occasionally called on to manage patients with penetrating cardiac injuries who arrive at the ED in extremis. Immediate thoracotomy in the ED is associated with good resuscitative results in a select group of such patients, but cardiorrhaphy is often impeded by frequent inflations of the left lung during resuscitation. We investigated a technique for selective right-lung ventilation using a standard single-lumen endotracheal tube in cadaver and animal models. This technique is easily applicable, provides adequate oxygenation and ventilation for up to 60 min, and expedites cardiorrhaphy in the ED.

Animals↗
PubMed1988

Effect of chronically-administered secretin on the nude mouse.

Secretin plays an important role in the growth regulation of certain cancers in vitro. The nude mouse is a suitable model for evaluation of the effects of this hormone on tumor xenografts in vivo, but little is known about long-term actions of secretin in this species. We investigated the impact of chronically administered synthetic porcine secretin in the nude mouse. Six groups of mice (eight animals each) received twice-daily intraperitoneal injections of saline or secretin at 0.5, 5, 50, 500, or 5,000 micrograms/kg for 14 days. Body weight and general health were unaffected by exogenous secretin, and no apparent behavioral effects were observed. Seven abdominal organs were examined at necropsy and all were histologically normal. The only organ that showed a weight change was the pancreas (13% decrease at the highest secretin dose). This was accompanied by decreases in DNA and RNA content, indicating pancreatic hypoplasia. Secretin administration caused changes in DNA and/or RNA content (but not protein content or weight) in liver, small bowel, cecum, and large bowel. No effect of secretin on stomach or kidney was observed. Our work demonstrates the safety of frequent injections of pharmacologic doses of secretin in this frail animal and suggests that the nude mouse is an appropriate model for the in vivo study of tumor growth regulation by secretin.

Animals↗
PubMed1988

Effect of chronically administered pentagastrin on the nude mouse.

The nude mouse has been used to evaluate the effect of gastrin on xenografted tissues, but little is known about long-term actions of gastrin on native organs in this species. We investigated the impact of chronically administered synthetic pentagastrin on the nude mouse. Six groups of mice (eight animals each) received intraperitoneal injections twice daily for 14 days with saline or pentagastrin at 0.5, 5, 50, 500, or 5,000 micrograms/kg. Behavior, overall health, and body weight were unaffected by this treatment. Of the seven organs examined at necropsy, only the pancreas showed a weight gain in response to pentagastrin treatment, and this occurred only at the highest dose. Total DNA content of the pancreas decreased in a dose-related manner, indicating hypoplasia, whereas pancreatic RNA content increased, indicating hypertrophy. No effect on the stomach was observed. This work indicates that the nude mouse is less sensitive than other species to visceral growth regulation by pentagastrin, and that toxicity is low.

Animals↗
PubMed1988

Tolerance of rat testis to graded periods of total circulatory isolation.

Infertility because of testicular damage is a distressing problem for survivors of cancer chemotherapy. We have previously described a cytoprotective effect of temporary testicular circulatory isolation (TCI) during doxorubicin administration in the rat. In this report we define the relationship between duration of TCI and testicular ischemic injury, using paired groups of animals with normothermic TCI and hypothermic TCI. Sixty rats were used and received TCI for varying lengths of time up to 180 minutes, with or without hypothermia. On day 56 +/- 4, all rats were killed and necropsied. Testicular injury was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulation index, and epididymal index. Warm TCI for up to 60 minutes induced modest damage to germ cells, while injury was greater with cold TCI. Leydig cells and vascular tissues were essentially unaffected by TCI, although Sertoli cell abnormalities were noted in rats receiving a long duration of TCI.

Animals↗
PubMed1987

Regional doxorubicin delivery reduces testicular toxicity.

Many anti-cancer drugs cause infertility. Regional delivery of these agents is a potential method to avoid this problem. We investigated the protective effect of normothermic testicular circulatory arrest on gonadal toxicity during doxorubicin administration in the Sprague-Dawley rat. Four groups of eight rats each were used. Animals in group 1 received no treatment. Rats in group 2 were anesthetized and received a bolus of intravenous doxorubicin (6 mg/kg). In groups 3 and 4, normothermic circulatory isolation of the left testis was induced by cross-clamping of the spermatic cord and gubernaculum immediately before doxorubicin administration. This was maintained for 15 min after doxorubicin administration in group 3 and for 45 min in group 4. Cessation and return of testicular blood flow were confirmed by Doppler. On Day 56, all rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by measurement of testicular weight, sperm count, repopulation index, and epididymal index. The results indicated that 15 min of testicular circulatory isolation mitigated testicular toxicity to a small extent and that 45 min of circulatory isolation provided moderate protection against doxorubicin-induced testicular toxicity.

Animals↗
PubMed1987

Exogenous cholecystokinin (CCK) reduces neonatal rat brain opioid receptor density and CCK levels.

Newborn rats were given saline or cholecystokinin8 (CCK8) (5 micrograms/kg, twice daily) i.p. for 3 weeks. On day 21, effects on brain development were assessed. CCK-like immunoreactivity was measured in 7 brain regions; a small (12-18%) but significant decrease in endogenous levels of this peptide was detected in cerebral cortex, medulla and pons of the CCK-treated rats. Morphometric measurements revealed a slight reduction in thickness of most cerebral cortical sections within the CCK-treated group. The area of a midsagittal section of the cerebellum was unchanged except for the Purkinje/granule cell layer, which was smaller in CCK-treated animals. Levels of mu-, delta- and kappa-opioid receptors were estimated by homologous displacement binding assays using selective radioligands. The CCK treatment resulted in a significant decrease in levels of mu- (11%) and delta- (13%)-sites in the cerebral cortex. Neither binding affinities nor kappa-receptor densities were altered. Other animals received the same treatment regimens for 21 days and were maintained for an additional 29 days without treatment; these rats had reductions only in cortical mu-sites (15%). Chronic intraventricular administration of CCK (0.1 microgram/h) to adult rats did not elicit a similar down-regulation of cortical mu or delta receptors, suggesting that the effects observed in neonates reflected developmental processes.

Animals↗
PubMed1987

Aortoesophageal fistula: case report and literature review.

Fistulous communication between the aorta and esophagus is a rare but usually fatal disorder. Esophageal foreign bodies have been reported to cause aortoesophageal fistula rarely. Spontaneous aortoesophageal fistula as a result of atherosclerotic disease of the aorta has not been reported. This article describes a case of aortoesophageal fistula caused by an ulcerated atherosclerotic plaque, which we believe is the first case report implicating such an etiologic factor.

Aged↗
PubMed1986

Tumor measurement in the nude mouse.

In this study, the pitfalls of tumor measurement in the nude mouse were evaluated. Regarding intermethod variation, diameters of subcutaneous tumors in nude mice were expressed as length, area, and volume; tumor weights were also recorded. These measurements were all compared to a reference standard: water displacement volume. Estimates of area and volume derived from caliper measurements correlated well with water displacement volume (r = 0.97 and 0.98, respectively). At necropsy, tumor weight was the most consistent and reproducible reflection of tumor volume (r = 1.0000). Regarding interobserver variation, mean absolute difference among volumes determined by several investigators who measured the same tumors in living animals was determined. This averaged 15% of the mean calculated volume. Regarding intraobserver variation, observers measured four separate masses in nude mice eight times each. The observers were prevented from realizing that the same animals were being repeatedly evaluated. Volumes were compared in order to quantify the average variation that occurs when a single investigator repeatedly measures the same mass. When large masses were measured, this error was 7%; when small masses were measured, the error was 27%. Recommendations are made for future work employing tumor measurement.

Animals↗
PubMed1986

Effect of liquid diet on nude mouse gastrointestinal tract.

The nude (athymic) mouse is currently used to study the effect of gastrin on cancer xenografts. We sought to develop a hypogastrinemia nude mouse model for use in evaluating the effect of hypogastrinemia on such xenografts. Thirty-six non-tumor-bearing nude mice were studied. Eighteen received a nutritionally complete liquid diet; eighteen received standard chow. Six mice from each group were weighed and killed (nonfasting) on days 2, 8, and 15. Mean serum gastrin levels (+/- SEM) for the control group were 118.7 +/- 7.5, 118.7 +/- 8.7, and 118.0 +/- 7.5 pg/ml on days 2, 8, and 15, respectively. Serum gastrin levels for the liquid diet group significantly decreased to 87.0 +/- 7.6, 88.0 +/- 9.7, and 66.7 +/- 9.6 pg/ml on the same days. Animals in both groups gained weight normally; there were no significant weight differences between the two groups at any point. No histological abnormalities were seen in stomach, small intestine, colon, cecum, liver, pancreas, spleen or kidney. However, the liquid diet group showed atrophic changes in colon: significant reductions in colon weight and RNA content on days 8 and 15, and significant reduction in colon protein content on day 8. This model of hypogastrinemia is reliable and inexpensive. The nonsurgical nature of the preparation allows excellent survival in this immunodeficient animal.

Animals↗
PubMed1986

Effect of chronically administered somatostatin on the nude mouse.

We investigated the impact of chronically administered synthetic cyclic somatostatin-14 on the nude mouse. Four groups of seven animals each received intraperitoneal injections twice daily for 14 days with diluent or 5, 50, or 500 mcg/kg somatostatin in hydrolyzed gelatin. Overall health and body weight were unaffected by this treatment. Among the seven organs examined at necropsy, kidney alone showed a dose-related gain in weight with increasing somatostatin dose. Renal RNA content also increased in response to somatostatin treatment, but liver DNA content and small bowel DNA content and protein content decreased. This work indicates that somatostatin affects metabolism of gastrointestinal tissues and provides evidence that renal growth can be regulated by somatostatin. Whether similar effects occur at a physiological somatostatin level is unknown, but the current findings suggest new therapeutic possibilities for this hormone.

Animals↗
PubMed1986

Testicular cytotoxicity of intravenous doxorubicin in rats.

Although the testicular cytotoxicity of many chemotherapeutic drugs has been evaluated in mice, their small size can pose technical problems. In this report, we describe doxorubicin-induced testicular toxicity in a larger animal model, the Sprague-Dawley rat. Fifty-three rats were used for this study. On day 0, rats in the treatment groups were anesthetized and given different single intravenous doses of doxorubicin (0.1 to 30 mg./kg.). On day 56 +/- 2, all surviving rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulation index and epididymal index. The histologic effects of doxorubicin on the heart, liver and kidney were qualitatively evaluated. Progressive dose-dependent testicular atrophy and oligospermia occurred at low and intermediate dosages of doxorubicin (0.1 to 5 mg./kg.). Marked testicular atrophy, oligospermia and germinal aplasia were observed at high dosage of doxorubicin (10 mg./kg.). LD50 for animal mortality at day 56 +/- 2 for doxorubicin appears to be 10 mg./kg. These findings are similar to those reported in mice. The rat is a suitable model for the study of techniques to avoid drug-induced testicular damage.

Animals↗
PubMed1985

Effect of cholecystokinin on human cholangiocarcinoma xenografted into nude mice.

Gastrointestinal polypeptide hormones regulate growth of various normal gastrointestinal tissues as well as certain visceral cancers. Since cholecystokinin (CCK) promotes growth of normal biliary tract, we sought to determine whether CCK affects the growth and metabolism of human cholangiocarcinoma line SLU 132. Twenty-six nude mice with s.c. xenografts of this cancer received either CCK octapeptide (50 micrograms/kg/dose) or 0.9% NaCl solution (saline) twice a day i.p. for 14 days. Tumor volume was calculated from Vernier caliper measurements. At sacrifice on Day 15, tumors were excised, weighed, and examined histologically. DNA, RNA, and protein were measured in the xenografted carcinomas. Because this cholangiocarcinoma produces carcinoembryonic antigen (CEA), we obtained serum at sacrifice for CEA radioimmunoassay and also tumor tissue for CEA immunolabeling with murine anti-CEA monoclonal antibody. Serum CEA levels were 90% higher in the CCK-treated group. Tumor tissue in the CCK-treated group also contained more CEA than did the controls. Mean tumor volume increased significantly in the saline group during the 14-day treatment period, whereas mean tumor volume did not increase significantly in the CCK group. Exogenous high-dose CCK thus appears to increase production and release of CEA from SLU-132; it also appears to retard growth of this tumor line in the nude mouse.

Adenoma, Bile Duct↗
PubMed1985

Pancreatic oncofetal antigen in the detection of experimental cancer of the pancreas.

A hamster serum protein which reacted with anti-human pancreatic oncofetal antigen (POA) was identified in sera from hamsters with varying types of pancreatic pathology. Hamsters were treated with N-nitrobis-(2-hydroxypropyl)-amine, and histological findings in the pancreas were correlated with hamster POA. The cross reactivity of anti-human POA with hamster POA was poor. As a result, the sensitivity of this assay was too low to permit its use in serologically discriminating carcinogen-induced pancreatic cancer from other pancreatic pathologies. A specific antiserum and assay system to hamster POA may overcome this problem.

Animals↗