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Biomedical subjects

L E Fox

Publications and source records attributed to L E Fox.

At least 55 records · Page 3Linked to original sources

A bleeding disorder (von Willebrand's disease) in a Himalayan cat.

A bleeding disorder (von Willebrand's disease) was diagnosed in a 9-year-old male Himalayan cat examined because of persistent oral bleeding after routine dental extraction. Bleeding subsided after empirical treatment, which included prednisolone, vitamin K1, and transfusion of fresh blood, but recurred spontaneously after 8 months of apparent good health. Pertinent results of routine laboratory testing included an inconstant prolongation of the activated partial thromboplastin time and recurring iron-deficiency anemia. Assays of specific coagulation factors revealed low factor VIII coagulant activity and undetectable factor VIII-related antigen, a pattern considered to be diagnostic of von Willebrand's disease. This condition, not previously reported in a cat, should be included in the differential diagnosis when cats are examined because of abnormal bleeding.

Anemia, Hypochromic↗

Microtubular protofilaments and subunits of the outer dynein arm in cilia from dogs with primary ciliary dyskinesia.

Using a procedure of membrane solubilization followed by tannic acid fixation-staining, we found abnormally constructed central and B microtubules in cilia from dogs with primary ciliary dyskinesia. We also found that a ciliary abnormality commonly associated with primary ciliary dyskinesia, "shortened outer dynein arms," actually represents the absence of a specific set of the 3 peripheral subunits that make up the outer dynein arms. We believe that this is the first time that these have been reported. Because the proximal subunits of the outer dynein arm are present and attached to the A microtubule, we argue that in these patients there is no structural abnormality of the A microtubule or the A-tubule attachment sites for outer and inner arms and radial spokes. Also, because a majority of cilia in these patients were motile, we believe that the data from this study support the concept that the outer dynein arms are not required for some motion but probably required for normal motility; however, the central microtubules, central microtubular complex, and probably the B tubules are essential for motility.

Adenosine Triphosphatases↗

Developmental regulation of glutamine synthetase and carbonic anhydrase II in neural retina.

Glutamine synthetase (GS) is expressed in the neural retina only in Muller glia cells and is inducible with cortisol. A chicken genomic clone that contains at least part of the coding region for the GS enzyme was used to investigate developmental changes in the level of GS mRNA in embryonic chicken retina. A major GS transcript (approximately equal to 3 kilobases) detected by the probe begins to accumulate sharply on day 15 of embryonic development. When cortisol is prematurely supplied to early embryonic retina, it induces precocious accumulation of GS mRNA and of the GS enzyme. At later ages, these effects of cortisol are significantly greater, which suggests that competence to transcribe or stabilize GS mRNA in response to stimulation with cortisol increases with development. Carbonic anhydrase II (CA-II) is expressed in early retina in all the cells, but it becomes later restricted to Muller glia. Using cloned CA-II cDNA, we detected a high level of CA-II mRNA in early retina, followed by a decline due to arrest of CA-II mRNA accumulation in differentiated neurons. As glia cells mature, CA-II mRNA and the enzyme increase to a new high level. Therefore, changes in CA-II gene expression during retina development reflect differentiation-dependent cell-type-specific control of CA-II mRNA accumulation.

Age Factors↗

Accumulation of c-src mRNA is developmentally regulated in embryonic neural retina.

Accumulation of c-src mRNA gradually increased during early development of the neural retina in chicken embryos and reached a peak by days 11 to 13 of embryonic life. Thereafter, its amount declined to a low level which persisted also in adult retina. The early increase in c-src mRNA correlated inversely with the decrease in the amount of H3.2 replication histone mRNA and with the decline in the rate of cell growth. The accumulation profile of c-src mRNA corresponded to that of pp60c-src protein, suggesting that the latter is regulated at the level of transcription.

Animals↗

Changes in patterns and synthesis of proteins in embryonic neural retina studied by 2-dimensional gel electrophoresis.

Changes in protein patterns during early differentiation of embryonic neural retina (chick) were studied by 2-dimensional gel electrophoresis. The procedures employed here made it possible to visualize the overall population of proteins present in the tissue at a given time and, on the same gel to distinguish labeled from unlabeled proteins. 2-Dimensional gels were stained by a highly sensitive silver stain to visualize, map and quantitate proteins (and polypeptides) resolved by electrophoresis; the same gels were then autoradiographed in order to differentiate between actively synthesized and pre-existing proteins at each development stage. The effectiveness of this combinative analysis was first verified by identifying and localizing glutamine synthetase, an inducible enzyme marker of retina differentiation. Next, protein patterns in retina tissue at 2 embryonic ages were compared. Of the large number of spots visualized by the above methods approximately 10% showed distinct qualitative-quantitative developmental changes; these were grouped into 7 classes representative of major modes of alteration of protein patterns during cell differentiation.

Animals↗

Primary ciliary dyskinesia in the dog.

Electron microscopy was used to diagnose primary ciliary dyskinesia in a litter of English pointer dogs and in a golden retriever dog. A technique of membrane solubilization, fixation, and negative staining with glutaraldehyde tannic acid identified abnormally constructed central and B microtubules in respiratory cilia from dogs with primary ciliary dyskinesia. Shortened outer dynein arms commonly associated with primary ciliary dyskinesia actually represents the absence of a specific subset of the three most peripheral components of the whole outer dynein arm structure.

Animals↗

Plasma histamine and gastrin concentrations in 17 dogs with mast cell tumors.

Dogs with mast cell tumors (MCT) are often affected with paraneoplastic syndromes such as gastrointestinal ulceration. The mechanism of ulceration is believed to be related to hyperhistaminemia. To test this hypothesis, plasma histamine and gastrin concentrations were measured in 17 dogs with MCT. Plasma histamine concentrations in dogs with MCT were significantly higher than those in normal dogs. Conversely, plasma gastrin concentrations in dogs with MCT were significantly lower than gastrin concentrations in normal dogs. Additionally, plasma gastrin concentrations were inversely related to plasma histamine concentrations, which provided indirect evidence for the presence of hyperacidity secondary to hyperhistaminemia (r2 = 57.7). Plasma histamine and plasma gastrin concentrations were not related to clinical stage of disease, tumor histologic grade, or tumor size. Median survival time was 245 days, with a range of 90 to 1315 days. Because the degree of hyperhistaminemia could not be predicted in this study from the clinical stage, histologic grade, or tumor size, these data suggest that hyperhistaminemia may occur in any dog with MCT.

Animals↗

Evaluation of L-asparaginase: polyethylene glycol conjugate versus native L-asparaginase combined with chemotherapy. A randomized double-blind study in canine lymphoma.

L-asparaginase is an enzyme that inhibits protein synthesis by the depletion of sources of L-asparagine, which is necessary for transformed lymphoid cells to proliferate. L-asparaginase is used in the treatment of childhood acute lymphoblastic leukemia. A problem with L-asparaginase therapy is the immunogenicity of the enzyme and the development of anaphylactic reactions. Canine lymphoma is a predominantly B-cell tumor with widespread disease; without treatment, dogs with lymphoma usually survive 1-2 months. Canine lymphoma will respond to L-asparaginase therapy. A randomized double-blind study evaluated a polyethylene glycol (PEG) conjugate L-asparaginase combined with chemotherapy (vincristine, cyclophosphamide, doxorubicin, and prednisone). Thirty-five dogs were randomized to the PEG L-asparaginase group, and 34 dogs were randomized to the native L-asparaginase group. Thirty dogs (85.7%) achieved a complete remission (CR) with a median time to relapse of 217 days, and 32 (94.1%) dogs in the native L-asparaginase group achieved a CR with a median time to relapse of 214 days (P greater than 0.05). The asparaginase was well tolerated in both groups. Two dogs in the native L-asparaginase group had severe allergic reactions, and one dog in the PEG asparaginase group had a generalized urticarial reaction after repeated injections. This study indicates that PEG L-asparaginase has equal therapeutic efficacy to native L-asparaginase.

Animals↗

Evaluation of prognostic factors and sequential combination chemotherapy with doxorubicin for canine lymphoma.

Fifty-five dogs with lymphoma were treated using a doxorubicin-based sequential combination chemotherapy protocol. Complete response, partial response, and no response were seen in 46, 4, and 5 dogs, respectively. The overall median remission duration and survival times were 36 and 51 weeks, respectively. Age, sex, weight, World Health Organization stage, World Health Organization substage (i.e., a = not ill, b = ill), serum calcium concentration, blood urea nitrogen concentration, breed and protocol alteration secondary to toxicity were evaluated for prognostic significance. Univariate analysis of prognostic factors identified sex, World Health Organization substage, and serum calcium as statistically significant (P < or = .05) variables for both survival and remission duration. Upon multivariate analysis, only substage (P = .036) was a significant prognostic factor for remission duration, whereas, both substage (P = .006) and sex (P = .005) were significant prognostic factors for survival.

Animals↗

Cutaneous hemangiosarcoma in 25 dogs: a retrospective study.

Hemangiosarcomas confined to the skin and underlying muscle were surgically excised in 25 dogs. Tumors were staged based on their histological location (ie, dermal, hypodermal, and deep). Dermal (stage I) hemangiosarcomas were small, most commonly ventral-abdominal or prepucial in location, and were associated with prolonged survival times (median survival, 780 days). Tumors with hypodermal (stage II) and underlying muscular involvement (stage III) were grouped together because of their larger size, bruise-like appearance, lack of anatomic predilection, biological behavior, and shorter survival times (median survival of 172 and 307 days for dogs with stages II and III, respectively). We conclude that dermal hemangiosarcomas may be effectively treated with surgery alone, whereas hemangiosarcomas located within the hypodermal tissues bear a poor prognosis and warrant wide surgical excision with adjuvant chemotherapy.

Animals↗

Owner satisfaction with partial mandibulectomy or maxillectomy for treatment of oral tumors in 27 dogs.

Twenty-seven dogs with oral tumors were treated with either rostral mandibulectomy, partial mandibulectomy, or partial maxillectomy. Owner satisfaction with the respective surgical procedure was assessed by telephone survey; 85% of owners were satisfied with the decision to treat their dogs. The percentage of satisfied owners was directly proportional to the increase in pet life span. Although difficulty in eating was noted for 12 (44%) of 27 dogs, pain was perceived to be reduced by the surgery for most animals. All owners found the cosmetic appearances of their dogs acceptable after facial hair regrew. The quality of the pets' lives was perceived by the owners to be most improved after rostral mandibulectomy and least improved after partial maxillectomy.

Animals↗

Carboplatin.

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Animals↗