Biomedical subjects

L E Fox

Publications and source records attributed to L E Fox.

At least 37 records · Page 2Linked to original sources

PubMed1996

Evaluation of dogs and cats with tumors of the ear canal: 145 cases (1978-1992).

OBJECTIVE: To characterize the frequency, clinical signs, biologic behavior, and response to treatment of tumors of the ear canal in dogs and cats. DESIGN: Retrospective analysis of medical records. ANIMALS: Medical records of 81 dogs (48 malignant tumors, 33 benign tumors) and 64 cats (56 malignant tumors, 8 benign tumors). PROCEDURE: Data were analyzed for cats and dogs with malignant tumors, and risk factors were analyzed for their potential impact on survival time. RESULTS: Malignant tumor types most commonly reported included ceruminous gland adenocarcinoma, squamous cell carcinoma, and carcinoma of undetermined origin. Median survival time of dogs with malignant aural tumors was > 58 months, whereas that of cats was 11.7 months. A poor prognosis was indicated by extensive tumor involvement (dogs) and by neurologic signs at time of diagnosis, diagnosis of squamous cell carcinoma or carcinoma of undetermined origin, and invasion into lymphatics or blood vessels (cats). CLINICAL IMPLICATIONS: Malignant tumors of the ear canal in dogs and cats have a propensity for local invasion, but tend not to metastasize. Squamous cell carcinoma and carcinoma of undetermined origin were the most locally aggressive tumors. Malignant tumors of the ear canal are best managed by aggressive surgical excision. Radiotherapy may be useful when tumors cannot be completely removed.

Adenocarcinoma↗

PubMed1995

Disseminated subcutaneous Mycobacterium fortuitum infection in a dog.

A 15-month-old 27.7-kg sexually intact male Doberman Pinscher was examined because of multiple subcutaneous abscesses on the neck, trunk, and limbs that developed 2 months after a dog bite and were refractory to antibiotic treatment. Incubation of a biopsy specimen at 37 C on a Lowenstein-Jensen agar slant for 8 days yielded growth of a Runyon's Group IV mycobacterium, and disseminated subcutaneous Mycobacterium sp infection was diagnosed. The organism was identified as M fortuitum, and was susceptible to amikacin, doxycycline, cefoxitin, minocycline, trimethoprim/sulfadiazine, and sulfisoxazole. Lesions resolved after 8 months of treatment with doxycycline (5 mg/kg of body weight, PO, q 12 h). The cause of dissemination was unknown; however, delay in debridement of the bite wound and corticosteroid use in initial wound management may have potentiated dissemination.

Abscess↗

PubMed1995

Feline cutaneous and subcutaneous neoplasms.

This article contains practical information about the more common feline skin tumors and an update on recent treatments. The tumor type, gross appearance, clinical behavior, prognosis, and treatment are provided.

Adenocarcinoma↗

PubMed1995

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine for the treatment of feline mammary adenocarcinoma--a multicenter randomized double-blind study.

Forty cats with previously untreated, histologically confirmed mammary gland adenocarcinoma received a radical mastectomy of the affected mammary chain(s). All cats were stratified according to clinical stage and randomized to receive either weekly intravenous liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or placebo (lipid-equivalent) for eight consecutive weeks in this double-blind study. Thirty-six of the 40 cats were available for follow-up. No significant differences in either disease-free interval or survival were found as a result of treatment. Cats with clinical stage II disease had a statistically significantly longer disease-free interval (p < 0.02), and overall survival (p < 0.005) when compared with clinical stage III cats.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1995

Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin.

Two randomized, double-blind clinical trials in dogs with spontaneous appendicular osteosarcoma treated with combination chemoimmunotherapy are reported. In both trials, dogs without overt metastasis underwent complete amputation of the affected limb. In trial 1, 40 dogs were treated with cisplatin chemotherapy [(CDDP), 70 mg/m2 i.v. every 28 days x 4]. Following CDDP, dogs without evidence of overt metastasis (n = 25) were randomized to receive liposome-encapsulated muramyl tripeptide phosphatidylethanolamine ](L-MTP-PE), 2 mg/m2 i.v.) or placebo liposomes (lipid equivalent) twice weekly for 8 weeks. Of 14 dogs in the placebo group, 13 (93%) died of metastasis; the median survival time was 9.8 months. Of 11 dogs in the L-MTP-PE group, 8 (73%) developed metastasis; the median survival time was 14.4 months, which was significantly longer than that of the placebo group (P < 0.01). In trial 2, 64 dogs received CDDP (70 mg/m2 i.v. every 21 days x 4) and were randomized to concurrently receive L-MTP-PE (2 mg/m2 i.v.) twice or once weekly, or placebo liposomes once weekly for 8 weeks. Median survival times were 10.3, 10.5, and 7.6 months, respectively. There were no significant differences among the three treatment groups in trial 2. Survival times for dogs receiving L-MTP-PE in trial 1 were significantly longer than those for dogs in trial 2 that received four doses of CDDP concurrently with twice weekly L-MTP-PE (P < 0. 04). The results of the first trial confirm our previous observation that L-MTP-PE has antimetastatic activity in dogs with osteosarcoma when given following amputation. The results of the second trial demonstrate that there is no survival advantage of administering L-MTP-PE concurrently with CDDP.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1994

Developmental changes in the expression and compartmentalization of the glucocorticoid receptor in embryonic retina.

Inducibility by glucocorticoids of the glutamine synthetase gene in chicken embryo retina and the transcriptional activity of the glucocorticoid receptor (GR) greatly increase between embryonic days 6 and 10 (E6, E10), although the level of GR does not markedly change during that time. This apparent discrepancy was investigated by examining the pattern of GR expression in undifferentiated E6 retina and in E10 retina, which consists mostly of differentiated cells. Two GR isoforms, 90 and 95 kDa, were found to be expressed at both of these ages at a similar total level but in different proportions: in E6 retina the level of the 90-kDa isoform was higher, whereas in E10 retina the 95-kDa receptor was higher. However, following treatment of the retinas with cortisol, the 95-kDa isoform became the predominant receptor at both ages. Immunohistochemical analysis revealed that the cellular localization of GR markedly changed in the course of development: in the undifferentiated E6 retina GR was expressed in virtually all cells, whereas in the more differentiated E10 and E12 retina, GR was detected only in Müller glia cells. The latter represent approximately 20% of the cells in this tissue and are the only cells in which glucocorticoid hormone induces the glutamine synthetase gene. We suggest that the compartmentalization of GR in Müller glia is a major aspect of the mechanism that modulates receptor activity during retina development and results in the temporal increase in the inducibility of glutamine synthetase and its specific localization in Müller glia cells.

Animals↗

PubMed1994

Molecular basis for differential expression of glutamine synthetase in retina glia and neurons.

Glutamine synthetase (GS) is a differentiation marker of retina glial cell. It is expressed in the chicken neural retina at a particularly high level, is inducible by glucocorticoids and is always confined to Müller glia. This study investigated the molecular basis for tissue and cell-type specific expression of the GS gene. A high level of GS expression in the retina was found to coincide with the accumulation of a relatively high level of GS mRNA in this tissue. The gliatoxic agent alpha-aminoadipic acid, which can selectively destroy glia cells, was used to demonstrate that restriction of GS induction to Müller glia is controlled at a transcriptional level. Cortisol could induce accumulation of GS mRNA and transcription of the GS gene in Müller glia but not in retina neurons. Glia and neurons were also found to differ in their ability to express the glucocorticoid inducible CAT construct, p delta G46TCO, which is controlled by a 'simple GRE' promoter. When introduced into cells of retina tissue, this construct was cortisol-inducible in glia whereas in neurons it was only slightly inducible or not at all. Introduction of a glucocorticoid receptor expression vector into the cells facilitated induction of the CAT construct in neurons. Analysis by immunoblotting revealed that expression of the glucocorticoid receptor protein is predominantly restricted to Müller glia. These results suggest that differential levels of glucocorticoid receptor expression in glia and neurons might be the basis for cell-type specific induction of GS.

Animals↗

PubMed1994

Induction of serum tumor necrosis factor-alpha and interleukin-6 activity by liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) in normal cats.

Tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) are products of activated monocytes/macrophages with anti-tumor activity. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) is a potent monocyte/macrophage activator. Sera from cats after intravenous L-MTP-PE administration showed TNF alpha activity using a WEHI-164 cell cytotoxicity assay and IL-6 activity using an IL-6 dependent mouse 7TD1 hybridoma cell proliferation assay. Serum TNF alpha activity peaked at 2 hours after L-MTP-PE administration. Significant differences from lipid-equivalent controls were observed at 2 and 3 hours (P < 0.05). Neutralization of serum TNF alpha activity was accomplished with serial dilutions of rhTNF alpha monoclonal antibody. Serum IL-6 activity peaked at 3 hours after L-MTP-PE administration. Significant differences from lipid-equivalent controls were observed at 2, 3, and 4 hours (P < 0.05). Neutralization of serum IL-6 activity was not achieved with goat anti-rhIL-6 polyclonal antibody. Intravenous L-MTP-PE, but not lipid-equivalent, induces serum TNF alpha and IL-6 activity in normal cats.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1994

Current studies of liposome muramyl tripeptide (CGP 19835A lipid) therapy for metastasis in spontaneous tumors: a progress review.

Targeted delivery of macrophage activating agents is an attractive approach to treat micrometastatic disease. Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a potent activator of monocytes/macrophages in humans, mice, and dogs. We have conducted clinical trials in dogs with malignant and highly metastatic spontaneous tumors. Presented are results of our trials evaluating L-MTP-PE in combination with surgery and chemotherapy in dogs with spontaneous osteosarcoma and hemangiosarcoma, particularly relevant malignancies having having many similarities to human cancer. Osteosarcoma dogs received chemotherapy following surgery (cisplatin q 28 days x 4). At completion of chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p < 0.021). Dogs with splenic hemangiosarcoma received combination chemotherapy following surgery (doxorubicin and cyclophosphamide q 21 days x 4). At the first chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p < 0.03). These studies show that L-MTP-PE is an effective agent for treatment of metastasis and can be safely administered in combination with chemotherapy.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1993

Molecular control of glutamine synthetase expression in the developing retina tissue.

Glutamine synthetase is a differentiation marker of the neural retina, whose expression is restricted to Müller glia cells, is inducible by glucocorticoids and is dependent on tissue development. The retina tissue acquires the competence to express GS in response to glucocorticoids with development, although the level of hormone binding activity in the cells does not alter with age. Using CAT constructs that are controlled by "simple GRE" promoters we demonstrated that glucocorticoid receptor transcription activity in retina cells increases with development. The increase in receptor activity correlates directly with the increase in inducibility of the glutamine synthetase gene and inversely with the rate of retina cell proliferation. At early developmental ages, when retina cells are still proliferating, the glucocorticoid receptor is transcriptionally inactive and glutamine synthetase expression cannot be induced. Receptor activity increases progressively with development and by day 12, when cell proliferation ceases, competence for glutamine synthetase induction is high. This competence for glutamine synthetase induction can be repressed by overexpressing the oncogene v-src, which stimulates retina cell proliferation. We discuss possible mechanisms for developmental-dependent modulation of glucocorticoid receptor transcriptional activity.

Animals↗

PubMed1993

Circadian regulation of iodopsin gene expression in embryonic photoreceptors in retinal cell culture.

A circadian clock regulates a number of diverse physiological functions in the vertebrate eye. In this study, we show that mRNA for the red-sensitive cone pigment, iodopsin, fluctuates with a circadian rhythm in chicken retina. Transcript levels increase in the late afternoon just prior to the time of cone disc shedding. Furthermore, iodopsin mRNA levels are regulated similarly by a circadian oscillator in primary cultures of dispersed embryonic chick retina. Nuclear run-on experiments show that the circadian regulation of iodopsin transcript abundance occurs at the level of gene transcription. Our results provide a demonstration of clock-regulated gene expression in a vertebrate preparation maintained in cell culture.

Animals↗

PubMed1991

Expression of v-src in embryonic neural retina alters cell adhesion, inhibits histogenesis, and prevents induction of glutamine synthetase.

Using Rous sarcoma virus as the vector, v-src or c-src genes were introduced into 6-day chicken embryo retina tissue in organ culture and their effects on retina development were investigated. Overexpression of c-src in many of the cells had no noticeable effect on retina development. In contrast, infection with v-src resulted in abnormal histogenesis and inhibition of differentiation. Although only a portion of the cells in infected tissue expressed the oncogene and displayed the transformation phenotype, the other cells were also hindered from becoming normally positioned and organized. Therefore, presence of oncogene-transformed cells within the tissue hindered organization and development of adjacent nontransformed cells. Failure of normal cell relationships impeded induction by cortisol of glutamine synthetase in Muller glia, which requires contact associations of the glia cells with neurons. The transformed cells tended to assemble into chaotic clusters, suggesting that their adhesiveness and contact affinities had become altered. This was confirmed by aggregation experiments with dissociated cells which showed that adhesiveness of transformed cells was greatly reduced and that they had lost the ability to cohere with nontransformed cells. In binary mixtures of transformed and nontransformed cells, the two sorted out into separate aggregates. Transformed cells formed loose clusters devoid of tissue architecture; aggregates of nontransformed cells became organized into retinotypic structures, and glutamine synthetase was inducible. Our findings suggest that the mechanisms of cell adhesion and cell affinities are a key target of v-src activity in infected cells and that modification of the cell surface may be a leading factor in other cellular changes characteristic of the v-src transformation phenotype.

Animals↗

PubMed1990

Biometric variables in patients with occludable anterior chamber angles.

Biometric studies of the ocular dimensions in eyes with narrow anterior chamber angles provide insight into the pathophysiology of pupillary block and may show which eyes are more prone to develop angle-closure glaucoma. We reviewed the records of 56 patients with occludable angles examined between 1980 and 1984. Initial biometric data obtained on the patients included corneal diameter, anterior chamber depth, lens thickness, and ocular axial length. The average length of follow-up was five years. Of 54 patients with complete clinical records, 20 (37%) eventually required peripheral iridectomy after a mean duration of 16 months from the initial examination. Cox's survival analysis showed a strong correlation between shortened duration to peripheral iridectomy and increasing lens thickness/ocular axial length ratio factor (P = .03). No other variables were significantly related to outcome. This suggests that the lens thickness/ocular axial length ratio may be useful as a predictor of clinical outcome in narrow-angle glaucoma.

Anterior Chamber↗

PubMed1990

Malignant jugulotympanic paraganglioma in a dog.

An invasive malignant epithelial neoplasm was diagnosed as a paraganglioma by light and electron microscopy and immunohistochemically by a positive reaction with anti-neuron-specific enolase. Due to the extensive involvement of the middle ear, a primary origin in the jugulotympanic or jugular paraganglia is suggested.

Animals↗

PubMed1989

The effect of pH on the viability of hypothermically stored rat hepatocytes.

Hepatocytes isolated from the rat liver were stored for up to 72 hr at 4 degrees C in a tissue culture medium (Liebovitz-15) at different pH values to determine how pH affects hepatocyte viability. This is a model to simulate cold storage of livers for transplantation and determine the optimal pH for maintenance of liver cell function. The cells were stored in the absence of oxygen. At the end of cold storage the percentage of the total cellular LDH released into the extracellular medium was used as a measure of hepatocyte viability. Also, lactate dehydrogenase (LDH) release was determined in hepatocytes incubated at normothermia (37 degrees C) for 90 min following 72 hr of cold storage. The results demonstrate that hepatocytes tolerate a wide range of pH values in the storage medium and that only about 10% of the total LDH was released from hepatocytes stored up to 72 hr at pH's from 5.0 to 8.0. Normothermic incubation, however, demonstrated that the pH of the storage medium affected viability. After 48 hr of storage only hepatocytes stored at pH values from 7.0 to 8.0 remained viable (LDH release similar to that of freshly incubated hepatocytes = 28 +/- 7.2%). After 72 hr of storage and 90 min of normothermic incubation, hepatocytes incubated at all pH values studied were nonviable (greater than 60% release of LDH). These results suggest that the optimal pH for storage of hepatocytes at 4 degrees C is near neutrality (7.0 to 7.4).

Animals↗

PubMed1989

Hypothermic preservation of hepatocytes. I. Role of cell swelling.

Hepatocytes from isolated rat livers were hypothermically incubated (5 degrees C) in an oxygenated environment with continuous shaking (to simulate organ perfusion preservation). The incubation solution was either a tissue culture medium (L-15), an organ preservation perfusate (UW gluconate), or a simple cold-storage solution used for organ preservation (UW lactobionate). Hepatocyte viability was assessed from the release of lactate dehydrogenase (LDH) into the incubation medium. Cell swelling (due to the uptake of water) was also measured. Within 24 hr, hepatocytes hypothermically stored in each of the three incubation solutions became swollen (30 to 40% water gain) and lost a significant amount of LDH (as much as 60%). The addition of polyethylene glycol (PEG; relative molecular mass 8000; 5 g%) to the solutions suppressed cell swelling and allowed the incubated hepatocytes to remain relatively well preserved (30% LDH release) for as long as 120 hr. Adding either dextran (relative molecular mass 10,000 to 78,000; 5 g%) or saccharides (100 mmol/liter) instead of PEG neither prevented cell swelling nor prevented the cells from dying. The results of this study suggest (i) there is a direct correlation (r = 0.873) between hypothermia-induced cell swelling and cell death (i.e., the suppression of cell swelling prevents cell death); (ii) the mechanism by which PEG prevents cell swelling (and thus maintains cell viability) is not related to the osmotic or oncotic properties of the molecule but instead is apparently related to some unknown interaction between PEG and the cell, an interaction that provides stability during hypothermic incubation; and (iii) hypothermia-induced cell swelling must be prevented if isolated hepatocytes are to be used as a model for studying the mechanism by which cell damage occurs during hypothermic organ preservation. By eliminating cell death due to cell swelling, the biochemical mechanisms of cell death can be studied.

Animals↗

PubMed1988

Neoplastic angioendotheliomatosis in a dog: an angiotropic lymphoma.

Neoplastic angioendotheliomatosis was diagnosed in a nine-year-old, intact male German Shorthaired Pointer exhibiting progressive neurological signs over a six-month period. At necropsy, there was multifocal asymmetric, hemorrhagic necrosis within the cerebral hemispheres, centrum semiovale, caudate nucleus, and internal capsule. Histologically, there was extensive intravascular proliferation of pleomorphic mononuclear cells within the brain and multiple parenchymatous organs. Transmission electron microscopy demonstrated the absence of intercellular junctions between neoplastic cells. These cells were not attached to the vascular lining endothelium; Weibel-Palade bodies and a basement membrane were lacking. By indirect immunofluorescence, positive cytoplasmic staining of intravascular neoplastic cells for IgG was demonstrated. Peroxidase-antiperoxidase technique for Factor VIII related antigen was negative. As in man, this rare neoplastic disorder appears to be a lymphoma, apparently of the B cell line.

Animals↗

PubMed1987

Reversal of ethylene glycol-induced nephrotoxicosis in a dog.

Ethylene glycol-induced nephrotoxicosis was diagnosed in a dog with acute renal failure. Histologically, the dog had proximal tubular degeneration and necrosis, intraluminal calcium oxalate crystals, generally intact tubular basement membranes, and evidence of tubular regeneration. After 20 days of peritoneal dialysis and diuresis, renal function was adequate to maintain homeostasis without supportive care. Nine weeks after onset of the ethylene glycol-induced renal failure, the dog's kidneys were histologically and functionally normal.

Acute Kidney Injury↗