Search PubMed⌕ Search

Biomedical subjects

J R Leininger

Publications and source records attributed to J R Leininger.

At least 37 records · Page 2Linked to original sources

Adaptation of a colorimetric microtitration assay for quantifying Pasteurella haemolytica A1 leukotoxin and antileukotoxin.

A colorimetric microtitration assay was adapted to quantify the cytotoxicity of Pasteurella haemolytica A1 leukotoxin to bovine neutrophils used as target cells. The viability of leukotoxin-treated target cells was detected by use of a tetrazolium dye that living cells reduced to dark blue formazan. The amount of formazan formed (which was quantified by use of an ELISA plate reader) was directly proportional to the number of viable target cells. This assay system also was used to measure leukotoxin-neutralization antibody titers of bovine serum and lung lavage specimens obtained during vaccination experiments. The major advantages of this assay over other methods such as the 51Cr-release and trypan blue-exclusion assays are precision, rapidity, and low cost; it also does not use radioisotopes.

Animals↗

Measurement of Pasteurella haemolytica-specific lung and serum antibodies by ELISA.

The modified enzyme-linked immunosorbent assay (ELISA) was used to determine the relative quantities of class-specific antibodies to Pasteurella haemolytica. IgG1, IgG2 and IgA were present in significantly higher quantities in bronchoalveolar washings (BAW), but in decreasing quantities, respectively; IgM was present in very low amounts. IgM, IgG1 and IgG2 were present in serum, again in decreasing quantities, respectively. IgA antibody quantities were lowest in serum. The indirect antibody ELISA was found to be superior to the indirect bacterial agglutination (IBA) technique for determining antibody titres against P. haemolytica.

Agglutination Tests↗

Medical dissolution of canine struvite uroliths.

Medical therapy is an effective method of canine struvite urolith dissolution. Recommendations include (1) eradication or control of urinary tract infection (if present), (2) use of calculolytic diets, and (3) administration of urease inhibitors to patients with persistent urinary tract infection caused by urease-producing microbes.

Animals↗

Voluntary exercise and its effects on young SHR and stroke-prone hypertensive rats.

To determine whether voluntary exercise would lower resting blood pressure in spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SP-SHR), two separate but interrelated investigations were undertaken. The studies were initiated when the animals were 28-35 days of age and after they were assigned to either activity or sedentary cages. The activity cages were connected to transducers and recorders that allowed the monitoring and calculation of frequency, duration, and running speed. The SHR group ran 3-7 km/day intermittently for 12 wk at high speeds (48-68 m/min), which resulted in heart rates in excess of 500 beats/min. When the SHR exercised, they seldom exceeded 33 revolutions/bout (37 m) with the majority being less than 22 revolutions/bout. This type of exercise training significantly lowered, but did not normalize, resting blood pressure by approximately 20 mmHg [nontrained (NT) = 185 +/- 5; trained (T) = 163 +/- 5 mmHg] while increasing maximum O2 consumption (VO2max) (NT = 78 +/- 2.6; T = 95 +/- 2.2 ml X min-1 X kg-1) and endurance run time (NT = 62 +/- 9.0; T = 286 +/- 15.0 min), respectively. Although SP-SHR exhibited comparable patterns of voluntary activity, the effects were not similar. First, after approximately 5 wk of consuming a special Japanese rat chow and a 1% NaCl drinking solution, cerebrovascular lesions occurred and deaths ultimately resulted in both exercising and sedentary groups. Second, although there was statistical evidence for a training effect (higher VO2max, longer VO2 test run times), voluntary exercise had no advantage in either male or female runners in lowering resting blood pressures or in improving their life-spans. Whereas voluntary activity wheel exercise or moderate forced treadmill exercise will lower resting blood pressures in young SHR populations, similar generalizations cannot be made with young SP-SHR rats.

Animals↗

Teratogenic effect of acetohydroxamic acid in clinically normal beagles.

Acetohydroxamic acid (AHA), a potent urease inhibitor used for treatment of infection-induced struvite urolithiasis, was teratogenic after administration of 25 mg of AHA/kg of body weight/day orally to 5 clinically normal Beagles from the onset of proestrus until parturition. Thirty pups exposed to AHA in utero developed anomalies of the skeletal system, heart, and ventral midline. Cardiac anomalies included atrial septal defects (20%), ventricular septal defects (3%), and atrial and ventricular septal defects (3%). Skeletal anomalies included coccygeal hemivertebrae and fused coccygeal vertebrae (50%), supernumerary vertebrae (67%), supernumerary ribs (50%), duplicated sternebrae (3%), and lumbar hemivertebrae (3%). Defects of the ventral midline of the abdominal wall occurred in 20% of AHA-exposed pups. Other abnormalities included retarded growth, high neonatal mortality, and a decreased number of circulating RBC, compared with those in 30 control pups born to 5 Beagles given a placebo. Adverse effects of AHA in pregnant Beagles were limited to morphologic alterations (Howell-Jolly bodies, spherocytes, and target cells) in a small number of circulating RBC. Slight neutrophilic leukocytosis and monocytosis occurred between 0 and 30 days of pregnancy in dogs given AHA, compared with those in controls. Seemingly, AHA did not influence fertility, conception rate, or length of gestation.

Abnormalities, Drug-Induced↗

Pulmonary response to intratracheal challenge with Pasteurella haemolytica and Pasteurella multocida.

Calves were inoculated intratracheally with 5 X 10(7), 5 X 10(8), or 5 X 10(9) colony forming units of either 18-hour stationary phase cultures or 4-hour log phase cultures of Pasteurella haemolytica. The log phase culture at all concentrations produced more severe clinical signs, hematological changes and pulmonary lesions at postmortem examination than did the corresponding stationary phase culture. More severe effects were seen with the larger doses especially with the log phase culture. Fibrinous bronchopneumonia with focal or multifocal necrosis was consistently produced by both the stationary and log phase cultures. To determine if this lesion was peculiar to P. haemolytica or whether it could be produced generally by rapidly growing Gram negative organisms, a 4-hour log phase culture of Pasteurella multocida was prepared in an identical manner to that used for the culture of P. haemolytica and given to calves intratracheally at the high bacterial dose (5 X 10(9]. The P. haemolytica produced more severe clinical, hematological and morphological changes than did the P. multocida. The lesions observed with P. multocida differed morphologically from those of P. haemolytica; there was a suppurative exudative component and minimal to no necrosis with P. multocida. It appears that an important pathogenic principle is produced by the rapidly growing P. haemolytica that causes it to produce a more severe clinical disease and more necrotizing pulmonary lesions than P. multocida.

Animals↗

Nephrotoxicity of S-(2-chloro-1,1,2-trifluoroethyl)glutathione and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine, the glutathione and cysteine conjugates of chlorotrifluoroethene.

The glutathione and cysteine conjugates of the nephrotoxin chlorotrifluoroethene, S-(2-chloro-1,1,2-trifluoroethyl)glutathione (CTFG) and S-(2-chloro-1,1,2-trifluoroethyl)cysteine (CTFC), are potent nephrotoxins in male rats. Morphological changes in the kidneys were observed 1.5 hr after giving 100 mumol/kg of CTFG (i.v.), and severe damage to the proximal tubules was evident 24 hr after treatment; this dose of CTFG caused a 100-fold increase in urine glucose excretion, a 10-fold increase in urine protein excretion and a 4-fold increase in blood urea nitrogen concentrations 24 hr after administration. Administration of 50 mumol/kg of CTFG or 100 mumol/kg of CTFC produced similar lesions and increases in urine glucose excretion rates and blood urea nitrogen concentrations. Administration of 10 mumol/kg of CTFG produced no discernable effect on the kidneys. CTFG and CTFC did not alter plasma glucose concentrations or plasma glutamate-pyruvate transaminase activities. CTFG and CTFC produced time- and dose-dependent loses of cell viability in isolated rat renal tubular cells. The toxicity of CTFG to isolated renal tubular cells was prevented by the gamma-glutamyltransferase inhibitor AT-125, and the toxicity of CTFC and CTFG to isolated cells was prevented by aminooxyacetic acid, an inhibitor of pyridoxal phosphate-dependent enzymes. Moreover, S-(2-chloro-1,1,2-trifluoroethyl)-DL-alpha-methylcysteine, which cannot be metabolized by pyridoxal phosphate-dependent enzymes, was not toxic to isolated renal tubular cells. The data presented support the hypothesis that the nephrotoxicity of chlorotrifluoroethene is due to the enzymatic formation of a glutathione conjugate, which is metabolized to the ultimate nephrotoxin by the sequential action of renal gamma-glutamyltransferase, cysteinylglycine dipeptidase and cysteine conjugate beta-lyase.

Animals↗

Evaluation of a calculolytic diet in female dogs with induced struvite urolithiasis.

The calculolytic effect of a diet designed to reduce the urine concentration of urea, P, and Mg was evaluated in female Beagles with induced urease-positive urinary tract infections and struvite urolithiasis and in female Beagles with induced sterile struvite urolithiasis. The reduced-protein calculolytic diet induced urolith dissolution in 5 of 6 infected dogs with struvite urolithiasis in 2 to 5 months (means = 14.4 weeks). At the end of 6 months, uroliths in comparable control dogs fed a maintenance diet were 5 times larger and 14 times heavier than at the beginning of the study. The calculolytic diet induced urolith dissolution in 6 of 6 noninfected dogs with struvite uroliths in 2 to 4 weeks (means = 3.3 weeks). Four uroliths in noninfected dogs fed the maintenance diet dissolved over a period of 2 to 5 months (means = 14 weeks). Urolith dissolution in dogs fed the calculolytic diet was associated with diet-induced diuresis, reduction in urine pH, reduction in urine concentration of urea ammonia, P, and Mg, and increase in urine titratable acidity. Consumption of the calculolytic diet was also associated with significant (P = less than 0.01) reduction in the serum concentration of urea and albumin and a significant (P = less than 0.01) increase in serum hepatic alkaline phosphatase activity. Concomitant occurrence of hydropic degeneration of hepatocytes indicated that these biochemical and morphologic changes were associated with dietary protein restriction.

Animals↗

The combined effects of asbestos ingestion and localized X-irradiation of the colon in rats.

We hypothesized that the normal bowel may afford some protection to tissue penetration of ingested asbestos, due to the mucus produced by goblet cells which normally coats the gut surface. To study this, we exposed localized segments of the colons of laboratory rats to X-irradiation. These animals were then divided into 3 groups which were fed either a diet containing 10% chrysotile asbestos, a diet containing 10% non-nutritive cellulose fiber, or a standard laboratory diet. Autopsies and histopathology were performed on all animals that died spontaneously and those that were killed at 350 days. Various types of inflammatory and degenerative lesions were commonly seen, but there was little difference in frequency between the diet groups. Five adenocarcinomas and two sarcomas were seen in the fiber groups (three tumors in the asbestos group and four tumors in the cellulose group) but no tumors were seen in animals on the standard diet. There was not a significant difference in tumor rates between the asbestos and cellulose groups, nor was there a significant difference between the combined fiber groups and the standard diet group. It was concluded that the x-ray treatment resulted in localized damage to the colonic mucosa and, therefore, theoretically disrupted the normal mucus coating allowing the potential for increased tissue penetration by the asbestos. Ingested asbestos did not increase the risk for tumor development and, therefore, does not seem to be co-carcinogenic or a tumor promoter in combination with disruption of mucus coating and localized X-irradiation.

Animals↗

Animal studies of potential chronic lung disease of workers in swine confinement buildings.

The pathologic changes in laboratory animals housed in a swine confinement building were studied to predict potential chronic health effects on persons working in these buildings. Rabbits and guinea pigs were maintained for 12 months either in a confined nursery-grower unit (test animals) or in conventional laboratory animal housing (controls). Necropsies and histopathologic examinations were performed on animals that died prematurely or were killed at termination of the study. Blood serum from the animals was examined for antibodies to extracts from swine confinement house dust. The confinement atmosphere was monitored for environmental pollutants. Concentrations of gases and dust in the air of the confinement building were comparable to those found in a typical swine confinement building. Pulmonic lesions seen in the test rabbits and guinea pigs included diffuse interstitial histiocytic pneumonia. Tracheal and nasal turbinate lesions included epithelial hyperplasia and metaplasia, with submucosal infiltration of plasma cells and heterophils. Blood from the test animals contained serum precipitins to dust extract from confinement houses. The presence of precipitins combined with the microscopic appearance of the lungs indicated that an immunologic process, such as hypersensitivity pneumonitis, may be used to explain the basis of the observed lung lesions. The tracheal and turbinate lesions are best explained as a reaction to a chronic low-grade irritation.

Agricultural Workers' Diseases↗

Influences of exercise intensity, age, and medication on resting systolic blood pressure of SHR populations.

The influence of exercise training on the resting caudal arterial blood pressures (RBP) of hypertensive rats is unclear despite numerous investigations by different investigators. To determine whether RBP values were influenced by the intensity and the initial age of the animal at the time of training, several studies were undertaken that involved more than 100 rats. When male and female rats were endurance trained for 24 wk at an O2 consumption in excess of 75% of their maximum (Vo2 max), RBP results from nontrained (NT) or trained (T) animals were not significantly different even though at several time periods the T animals had higher resting pressures. However, when exercising rats at an intensity level representing 40-60% of their Vo2 max, the T groups had consistently lower RBP than their NT controls during the majority of the experimental time periods. In addition exercising young (2-3 wk old) hypertensive-prone rats at a moderate intensity was associated with lower RBP within 4-6 wk after the initiation of training; however, exercise training could not normalize RBP. Reduced dosages (85% of normal) of antihypertensive medication, when combined with moderate training, was also associated with lower and "normal" RBP in male but not female rats. We conclude that moderate exercise at an early age when combined with subnormal dosages of antihypertensive medication holds promise for the normalization of RBP in male hypertensive rats of a genetic origin.

Aging↗

Neuroepithelial tumor of the optic nerve in a horse.

A nine-year-old horse was presented with severe exophthalmos of the right eye and a large mass in the vitreal cavity. The affected globe was enucleated and two months following surgery the horse was euthanized because of spread of the tumor into the calvarium producing compression of the brain stem and neurologic signs. Examination of tumor tissue by light and electron microscopic examination showed a mixed neoplasm of primitive neuroepithelium.

Animals↗