Effect of cellular fatty acid alteration on adriamycin sensitivity in cultured L1210 murine leukemia cells.

We have investigated the effect of cellular fatty acid alteration on Adriamycin cytotoxicity using the L1210 lymphoblastic leukemia cell line. Cells growing in Roswell Park Memorial Institute Medium 1640 with 5% fetal bovine serum were modified with respect to fatty acid composition by supplementing their growth medium with 32 microM docosahexaenoic acid (22:6) or oleic acid (18:1). A soft agar clonogenic assay was then used to assess survival following incubation with Adriamycin. When exposed to the drug at a concentration of 0.4 microM, cells grown in the 22:6-supplemented medium were more sensitive (min of drug treatment required to reduce survival by 63% on the exponential portion of the survival curve, 64.9 +/- 4.2 min) to the cytotoxic effects of Adriamycin than cells grown in unsupplemented medium (min of drug treatment required to reduce survival by 63% on the exponential part of the survival curve, 106 +/- 9.7 min) (p less than 0.005). Cytotoxicity of L1210 cells grown in 18:1-supplemented medium was similar to that of cells grown in unsupplemented medium (min of drug treatment required to reduce survival by 63% on the exponential part of the survival curve, 126.6 +/- 9.1 min). The heightened sensitivity to Adriamycin of cells whose medium contained 22:6 increased as the concentration of fatty acid used to supplement the growth medium was increased. The cytotoxicity was also a function of the concentration of Adriamycin from 0.1 to 1.6 microM. When compared to cells grown in unsupplemented medium, those grown in 22:6-supplemented medium contained 3- to 4-fold more polyunsaturated fatty acids in their phospholipids, with a resultant doubling in the mean number of double bonds per fatty acid molecule. These data demonstrate that modification of cellular fatty acid composition may dramatically affect the sensitivity of a tumor cell to Adriamycin.

Influence of rate of heating on thermosensitivity of L1210 leukemia: membrane lipids and Mr 70,000 heat shock protein.

We examined the effect of rate of temperature rise on the thermosensitivity of a murine lymphoblastic leukemia. L1210 cells suspended in RPMI 1630 medium:5% fetal bovine serum at pH 7.4 were heated from 37 degrees C-42 degrees C, or 44 degrees C over variable times (immediately, 30, 60, 120, 180 min) in a circulating water bath controlled by an electronic temperature programmer. Survival of the cells using a soft agar clonogenic assay was plotted against the time at final temperature so that a Do (min of heat required to reduce survival by 63% on the exponential portion of the survival curve) could be calculated as an estimate of thermosensitivity. Cells heated from 37 degrees C-42 degrees C over a time period of 30 min (10 degrees C/h) were less thermosensitive (Do 62.7 +/- 12.5 min) as compared to those exposed immediately to 42 degrees C (Do 38.5 +/- 2.2 min). Cells heated over a period of 180 min (1.6 degrees C/h) showed almost no death even after 4 h at 42 degrees C. Thermosensitivity of cells heated to several other high temperatures was also a function of rate of heating. This relative thermal resistance induced by slow heating was not a result of a change in membrane cholesterol content or fatty acid composition. Similarly, there was no difference between cells heated at slow and fast rates in cell cycle distribution or in cellular protein concentration. The major heat shock protein of Mr 70,000, which was induced by immediate heating, was not synthesized at the same high rate 1-12 h after heat treatment by the cells made thermotolerant with slow heating. We conclude that the thermosensitivity of this neoplastic cell can be altered considerably by the rate of heating. This alteration is not due to a change in membrane lipids. Furthermore, the heat shock protein at Mr 70,000 which was synthesized after immediate heating could not be demonstrated in the gradually heated L1210 leukemia cells.

Granulocytotoxic antibodies in a patient with propylthiouracil-induced agranulocytosis.

Agranulocytosis developed in a patient who was receiving propylthiouracil. Using a microgranulocytotoxicity assay, serum taken from the patient was shown to be strongly granulocytotoxic when tested against the patients granulocytes and those obtained from two of eight normal subjects. Tests for granulocyte agglutinins and for lymphocytotoxicity were negative. Granulocytotoxic activity decreased as the patient's peripheral granulocyte count recovered. Cytotoxicity was shown to be mediated by a complement-dependent IgM antibody.

Angles of inclination and anteversion in hip dysplasia in the dog.

The angles of inclination and anteversion of the femoral head and neck were measured on 150 limbs of 75 dogs. These hip angles were compared with pathoanatomic and radiographic scores of hip dysplasia. There was a minimal difference between dysplastic and healthy dogs in the angles of inclination and anteversion. It was concluded that in this series of dogs, hip angles did not have a part in the development of hip dysplasia.

Hypervitaminosis A in the dog.

Toxic effects of excessive vitamin A and of excessive vitamin ADE were studied in 9 mixed Labrador Retriever pups. Clinical signs were loss of body weight, dullness, emaciation, roughened coat, evident pain in limb joints, and retarded growth. Radiologic changes were decreases in overall length and thickness of long bones, development of osteophytes, periosteal reaction, and premature closure of epiphyses. Pathologic changes were degenerative epiphyseal plate, hemorrhage and exostotic proliferation of periosteum, fatty liver, and microcalculi in kidney. Toxic effects of excessive vitamin A did not appear to be so great when it was administered as vitamin ADE.

Association between pelvic muscle mass and canine hip dysplasia.

OBJECTIVE: To investigate the relationship between pelvic muscle mass and development and expression of canine hip dysplasia (CHD). DESIGN: Prospective study. ANIMALS: 5 Greyhounds with anatomically normal hip joints, 59 German Shepherd Dogs (23 with CHD, 24 with near-normal hip joints, and 12 with normal hip joints), and 18 German Shepherd Dog-Greyhound crossbreeds (7 with CHD, 6 with near-normal hip joints, and 5 with normal hip joints) between 12 and 47 months old in which pelvic muscle mass was evaluated. Pectineal muscle and hip joint development were evaluated in 25 German Shepherd Dogs at 8 and 16 or 24 weeks of age. PROCEDURES: For evaluation of pelvic muscle mass, individual pelvic muscles were weighed and hip joints were assigned a score on the basis of severity of degenerative changes. For evaluation of pectineal muscle development, muscle sections were stained and examined. RESULTS: Pelvic muscle mass was greatest in Greyhounds, intermediate in crossbred dogs, and smallest in German Shepherd Dogs. Differences in pelvic muscle mass among breeds were attributable to differences in weights of individual muscles. Hip score was negatively correlated with pelvic muscle mass and weights of selected pelvic muscles. Dogs with pectineal hypotrophy at 8 weeks of age had type-2 muscle fiber paucity or muscle fiber-type grouping at 16 or 24 weeks of age. At 8 weeks of age, hip joints were composed of multiple centers of ossification, and the acetabulum was largely cartilaginous. By 24 weeks of age, the pelvic bones were largely, although incompletely, fused. CLINICAL IMPLICATIONS: Diminished pelvic muscle mass in dogs with CHD and altered muscle fiber size and composition in 8-week-old dogs that subsequently develop CHD strongly suggest that abnormalities of pelvic musculature are associated with development of CHD. The complex development of the hip joint from multiple centers of ossification may make the joint susceptible to abnormal modeling forces that would result from abnormalities in pelvic muscle mass.

Canine hip dysplasia in German Shepherd Dog-Greyhound crossbreeds.

Nineteen German Shepherd Dog-Greyhound crossbreeds in 7 litters were evaluated by pathoanatomic and/or radiographic examination of their pelves when 12 to 24 months old (mean, 19 months). The prevalence of hip dysplasia in the crossbreeds was 42% (8/19). The prevalence of hip dysplasia in purebred German Shepherd Dog half-siblings in 16 litters produced by parents of the crossbreeds when mated to other German Shepherd Dogs was 35% (16/46). When numerical values were assigned to the pathoanatootmic and radiographic evaluations of the pelves, it was found that the severity of dysplastic changes in the crossbreeds were not significantly different from those changes in their purebred German Shepherd Dog half-siblings. It was concluded that selection for normal hips through mating German Shepherd Dogs with Greyhounds would be no more effective in lowering the prevalence of hip dysplasia than would selection within the German Shepherd Dog breed, which would be more desirable with regard to maintaining the standard of the breed.

Comparison of two surgical procedures for arthrodesis of the proximal interphalangeal joint in horses.

Arthrodesis of the proximal interphalangeal joint in horses, with 2 screws crisscrossing the joint, was compared with arthrodesis achieved by placement of 3 screws crossing the joint parallel to the long axis of the bone. The comparison was made by means of radiography, gross and histologic examinations, and motion evaluation. Additionally, the fused 1st and 2nd phalanges resulting from each method were subjected to breaking forces. Motion evaluation and direct examination of the fused area demonstrated that either procedure can be used to achieve arthrodesis consistently, and the breaking procedure indicated that the fused joints were as strong or stronger than areas penetrated by the cortical screws used in internal fixation. The fused area resulting from the parallel procedure was stronger than that from the crisscross procedure. The parallel procedure was easier, gave better alignment of 1st and 2nd phalanges, and was prone to less error in screw placement. It was concluded that arthrodesis by either procedure was satisfactory for treating osteoarthritis and related problems of the proximal interphalangeal joint in horses, but that the parallel procedure created a superior union between the 1st and 2nd phalanges during the first 120 postoperative days.

Acute leptomeningeal reaction to the subarachnoid injection of ethyl iodophenylundecylate in dogs.

The effects of the subarachnoid injection of ethyl iodophenylundecylate were observed serially in dogs. The results of neurologic examination and cerebrospinal fluid analysis as well as the gross and histologic apppearance of the brain and spinal cord were evaluated. In 8 dogs, progressive nonpurulent leptomeningitis peaked in 5 days and regressed thereafter. The reaction appeared to be related to the physical properties of ethyl iodophenylundecylate.

Routes of blood supply to the head of the Pekin duck.

The principal routes of blood flow to the head in birds are the common carotid arteries and their branches. However, additional routes exist, and these were identified in White Pekin ducks. Metallic mercury was infused into the ischiatic artery of euthanized ducks with occluded brachiocephalic arteries during direct fluoroscopic visualization. In 7 of 10 birds, mercury reached the head through anastosmoses between the dorsal intercostal rami of the aorta and the descending vertebral arteries. In one bird, an anastomotsis was also present between the external iliac artery and the pectoral trunk. In 3 birds, no connections between the aorta and branches to the head could be demonstrated. It is likely that a small blood flow can reach the head through these anatomotses but it probably constitutes an insignificant fraction of the total.

Otognathia with complete pharyngeal fistulae in an Angus calif.

An Angus calf affected with bilateral otognathia and complete pharyngeal fistulae is described. The cause could not be determined.