Amyloid deposition in 2 feline thymomas.

Two cases of feline thymoma with amyloid deposition were encountered between 1982 and 2010. Neoplastic cells were separated by abundant, pale eosinophilic, homogeneous material that was congophilic and birefringent. Ultrastructurally, the neoplastic cells were connected by desmosomes, and the extracellular deposits were composed of nonbranching, hollow-cored fibrils, 8-10 nm in diameter. In the case with sufficient archived tissue for additional sections, the amyloid remained congophilic following potassium permanganate incubation, and the neoplastic cells were immunoreactive for pancytokeratin. The histologic, histochemical, ultrastructural, and immunohistochemical features of both neoplasms are consistent with epithelial-predominant thymoma with the unusual feature of intratumoral amyloid deposition. The affinity of the amyloid for Congo red following potassium permanganate incubation is consistent with non-AA amyloid. The ultrastructural findings were consistent with amyloid production by the neoplastic epithelial cells.

Association of hypothyroid disease in Doberman Pinscher dogs with a rare major histocompatibility complex DLA class II haplotype.

Canine hypothyroid disease is similar to Hashimoto's disease in humans, which has been shown to be associated with human major histocompatibility complex (MHC) genes. We have collected 27 Doberman Pinschers affected with primary hypothyroid disease and compared their MHC class II haplotypes with 129 unaffected Doberman Pinschers. Three dog-leucocyte antigen (DLA) genes, DLA-DRB1, DQA1 and DQB1, were characterized by sequence-based typing and assigned to haplotypes for each dog. One rare haplotype was found at an increased frequency in the affected dogs compared to the unaffected dogs (Odds ratio = 2.43, P < 0.02). This haplotype has only been found in Doberman Pinschers and Labradors to date.

Evidence that post-tetanic potentiation is mediated by neuropeptide release in Aplysia.

Many neuromuscular and central synapses exhibit activity-dependent plasticity. The sustained high-frequency firing needed to elicit some forms of plasticity are similar to those often required to release neuropeptides. We wanted to determine if neuropeptide release could contribute to post-tetanic potentiation (PTP) and chose neuromuscular synapses in buccal muscle I3a to explore this issue. This muscle is innervated by two motor neurons (termed B3 and B38) that show PTP in response to tetanic stimulation. B3 and B38 use glutamate as their fast transmitter but express different modulatory neuropeptides. B3 expresses FMRFamide, a neuropeptide that only slightly increases its own excitatory junction potentials (EJPs). B38 expresses the small cardioactive peptide (SCP), a neuropeptide that dramatically increases its own EJPs. It was our hypothesis that SCP released from B38's terminals during tetanic stimulation mediated a component of PTP for B38. Because no antagonist to SCP currently exists, we used several indirect approaches to test this hypothesis. First, we studied the effects of increasing stimulation frequency during the tetanus or lowering temperature on PTP. Both of these changes are known to dramatically increase SCP release. We found that increasing the frequency of stimulation increased PTP for both neurons; however, the effects were larger for B38. Decreasing the temperature tended to reduce PTP for B3, while increasing PTP for B38. These results were consistent with known properties of SCP release from B38. Next we selectively superfused the neuromuscular synapses with exogenous SCP to determine if this would occlude the effects of SCP released from B38 during a tetanus. We found that exogenous SCP dramatically reduced PTP for B38 but had little effect on PTP for B3. Thus our results support the hypothesis that physiological stimulation of B38 elicits PTP that is predominantly dependent on the release of SCP from its own terminals. They also demonstrate that the mechanisms underlying PTP can be very different for two motor neurons innervating the same target muscle.

Severe calcinosis cutis associated with treatment of hypoparathyroidism in a dog.

A 6-month-old, female border collie was referred for evaluation of hypocalcemia, hyperphosphatemia, fever, and painful ventral abdominal skin. She had recently been treated intravenously and subcutaneously (SC) with a diluted 10% calcium gluconate solution. The medical evaluation supported the diagnosis of primary hypoparathyroidism, but the subsequent hospital course was complicated by severe calcinosis cutis, which caused extensive skin necrosis and marked debilitation. This patient illustrates that administration of a calcium gluconate solution SC can be associated with extensive morbidity when administered to hyperphosphatemic patients.

Effects of racing and training on serum thyroid hormone concentrations in racing Greyhounds.

OBJECTIVES: To determine the effects of racing and training on serum thyroxine (T4), triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations in Greyhounds. ANIMALS: 9 adult racing Greyhounds. PROCEDURE: Serum thyroid hormone concentrations were measured before and 5 minutes after a race in dogs trained to race 500 m twice weekly for 6 months. Resting concentrations were measured again when these dogs had been neutered and had not raced for 3 months. Postrace concentrations were adjusted relative to albumin concentration to allow for effects of hemoconcentration. Thyroid hormone concentrations were then compared with those of clinically normal dogs of non-Greyhound breeds. RESULTS: When adjusted for hemoconcentration, total T4 concentrations increased significantly after racing and TSH concentrations decreased; however, there was no evidence of a change in free T4 or total or free T3 concentrations. Resting total T4 concentrations increased significantly when dogs had been neutered and were not in training. There was no evidence that training and neutering affected resting TSH, total or free T3, or free T4 concentrations. Resting concentrations of T3, TSH, and autoantibodies against T4, T3, and thyroglobulin were similar to those found in other breeds; however, resting free and total T4 concentrations were lower than those found in other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Except for total T4, thyroid hormone concentrations in Greyhounds are affected little by sprint racing and training. Greyhounds with low resting total and free T4 concentrations may not be hypothyroid.

Use of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II), a liposomal cisplatin analogue, in cats with oral squamous cell carcinoma.

OBJECTIVE: To determine clinical response and toxic effects of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP) administered i.v. at escalating doses to cats with oral squamous cell carcinoma (SCC). ANIMALS: 18 cats with oral SCC. PROCEDURE: Cats that failed to respond to conventional treatment or had nonresectable tumors were included. Data included a CBC, serum biochemical analyses, urinalysis, cytologic examination of a fine-needle aspirate of enlarged lymph nodes, and thoracic and oral radiographs for clinical staging. A starting dose (75 to 100 mg/m2 of L-NDDP) was administered i.v.. At 21-day intervals, subsequent doses increased by the rate of 5 or 10 mg/m2. Response was evaluated every 21 days by tumor measurement and thoracic radiography. Quality of life was assessed by owners, using a performance status questionnaire. RESULTS: On average, cats received 2 treatments. Toxicoses included an intermittent, acute anaphylactoid-parasympathomimetic reaction, lethargy or sedation (< or = 24 hours), inappetence or signs of depression (< or = 72 hours), mild to moderate increase in hepatic enzyme activity, and melena. Pulmonary, renal, or hematopoietic abnormalities were not evident. Performance status surveys indicated normal behavior and grooming or decreased activity and self-care (19/20 assessments), ate well with or without assistance (15/20), and did not lose weight (15/20). Median survival time was 59.8 days (mean, 54.1 days). CONCLUSIONS AND CLINICAL RELEVANCE: L-NDDP was ineffective for treatment of cats with oral SCC. None of the cats had a complete or partial remission. Acute toxicoses and poor therapeutic response limit therapeutic usefulness of L-NDDP in cats, unless dosage, frequency, and administration procedures can be improved.

Role of cAMP in the short-term modulation of a neuromuscular system in aplysia.

Neuromuscular synapses in buccal muscle I3a of Aplysia are modulated by the small cardioactive peptide (SCP), a peptide cotransmitter that is intrinsic to the motor neurons, and by serotonin (5-HT) released from modulatory neurons that are extrinsic to the motor circuit. Although the modulation of excitatory junction potentials (EJPs) and contractions by 5-HT and SCP has been studied extensively in this muscle, little is known about the mechanisms that underlie the modulation. 5-HT and SCP, at 1 microM, were found to potently increase the level of cAMP in I3a. Therefore we investigated whether the activation of the cAMP pathway was sufficient to modulate EJPs and contractions. The direct activation of adenylyl cyclase with forskolin increased the level of cAMP, facilitated EJPs, and potentiated contractions. Indeed, the short-term effects of forskolin were very similar to all aspects of the short-term effects of 5-HT and SCP. Membrane-permeable cAMP analogues also mimicked the effects of 5-HT and SCP on EJPs and contractions. However, it seems likely that some effects of 5-HT are also mediated through other second-messenger pathways because low concentrations of 5-HT modulate EJPs and contractions but do not significantly increase cAMP levels in I3a. It is possible that lower concentrations of 5-HT function through receptors linked to protein kinase C (PKC) because phorbol, an activator of PKC, modulated EJPs and contractions without increasing the levels of cAMP. In conclusion, we provide evidence that pharmacological agents that activate the cAMP pathway mimicked most of the effects of 5-HT or SCP and that more than one second-messenger system appears to be involved in the modulation of the I3a neuromuscular system.

Immunohistochemical detection of p53 tumor-suppressor protein is a poor indicator of prognosis for canine cutaneous mast cell tumors.

Eighty-three canine cutaneous mast cell tumors were graded histologically and evaluated immunohistochemically for p53 tumor-suppressor protein expression. An avidin-biotin immunohistochemical protocol incorporated a rabbit polyclonal antibody (CM-1) directed against normal and mutant p53 protein. Positive staining was observed in 44.6% (37/83) of tumors and included 50% (12/24) of grade I (well differentiated) tumors, 46.9% (23/49) of grade II (intermediate differentiation) tumors, and 20% (2/10) of grade III (poorly differentiated) tumors. A statistically significantly higher proportion (P < 0.019) of tumors from the head and neck (83.3%, 10/12), stained positive for p53 than tumors from the thorax, back, abdomen, and axilla (39.4%, 13/33), legs (35.7%, 10/28), or prepuce, scrotal, or inguinal areas (44.4%, 4/9). No statistically significant difference between p53 labeling and histologic grade, breed, or tumor size was present. Survival data were available for 53/83 (63.9%) of dogs. Positive reactivity for p53 was observed in 47% (25/53) of tumors within this group, with 57.9% (11/19) of grade I, 43.3% (13/30) of grade II, and 25% (1/4) of grade III tumors labeled. Mean survival time for the 53 dogs was 12.1 months. The median survival time for dogs with grade III tumors or tumors >5 cm was statistically significantly shorter (P < 0.0001) than for dogs with grades I and II or smaller tumors. Although p53 protein abnormalities may play a role in tumor development or behavior in some canine cutaneous mast cell tumors, immunoreactivity was not associated with lack of tumor differentiation, tumor locations previously shown to demonstrate aggressive biological behavior, breed predisposition, or survival times.

Blurred vision during sexual arousal associated with narrow-angle glaucoma.

PURPOSE: To describe three women with narrow-angle glaucoma who had transient blurred vision during sexual arousal. METHOD: Case reports. RESULTS: Three women, aged 37, 45, and 55 years, were seen with bilateral narrow-angle glaucoma and were treated with bilateral laser iridotomy. In each patient, additional surgery was required to control the glaucoma. After establishing a rapport with her physician, each patient described transient blurred vision, from a few minutes to several hours in duration, which began during sexual arousal. This symptom resolved after peripheral iridotomy and, in one patient, after laser iridoplasty. CONCLUSION: The association of transient blurred vision with sexual activity may delay presentation of patients with symptomatic narrow-angle glaucoma.

Glutamate is a fast excitatory transmitter at some buccal neuromuscular synapses in Aplysia.

Studies of the modulation of synaptic transmission in buccal muscle of Aplysia were limited because the conventional fast transmitter used by a number of large buccal motor neurons was unknown. Most of the identified buccal motor neurons are cholinergic because they synthesize acetylcholine (ACh) and their excitatory junction potentials (EJPs) are blocked by the cholinergic antagonist hexamethonium. However, three large identified motor neurons (B3, B6, and B38) do not synthesize ACh and their EJPs are not inhibited by hexamethonium. To identify the fast excitatory transmitter used by these noncholinergic motor neurons, we surveyed putative transmitters for their ability to evoke contractions. Of the noncholinergic transmitters tested, glutamate was the most effective at evoking contractions. The pharmacology of the putative glutamate receptor is different from previously characterized glutamate receptors in that glutamate agonists and antagonists previously used to classify glutamate receptors had little effect in this system. In addition, glutamate itself was the most effective agent tested at reducing EJPs evoked by the noncholinergic motor neurons presumably by desensitizing glutamate receptors. Finally, immunocytology using an antiserum raised to conjugated glutamate in parallel with intracellular fills indicated that the varicose axons of these motor neurons were glutamate-immunoreactive. Taken together, these results indicate that the fast transmitter used by the noncholinergic neurons is almost certainly glutamate itself. This information should help us understand the role of transmitters and cotransmitters in the generation of feeding behaviors in Aplysia.

Gastric hemorrhage in dogs given high doses of methylprednisolone sodium succinate.

OBJECTIVE: To determine whether healthy dogs given high doses of methylprednisolone sodium succinate (MPSS) develop gastrointestinal tract ulcers and hemorrhage. ANIMALS: 19 healthy male hound-type dogs. PROCEDURE: Dogs were assigned randomly to intravenously receive high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, every 6 hours for a total of 48 hours; n = 10) or an equal volume of saline (0.9% NaCl) solution (9). Gastroduodenoscopy was performed before and after treatment. Endoscopic evidence of gross hemorrhage in the cardia, fundus, antrum, and duodenum of each dog was graded from none (0) to severe (3), and a total stomach score was calculated as the sum of the regional gastric scores. Number of ulcers were recorded. The pH of gastric fluid and evidence of occult gastric and fecal blood were measured. Food retention was recorded. RESULTS: Gastric hemorrhage was evident in all dogs after MPSS administration and was severe in 9 of 10 dogs but not visible in any dog after saline treatment. Occult gastric blood was detected more commonly (9/10 vs 2/9), median gastric acidity was greater (pH 1 vs pH 3), and food was retained more commonly (7/10 vs 1/9) in the stomach of MPSS-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: High doses of MPSS cause gastric hemorrhage in dogs. All dogs treated with high doses of MPSS should be treated with mucosal protectants or antacids to prevent gastric hemorrhage.

Efficacy of misoprostol in prevention of gastric hemorrhage in dogs treated with high doses of methylprednisolone sodium succinate.

OBJECTIVE: To determine whether administration of misoprostol prevents gastric hemorrhage in healthy dogs treated with high doses of methylprednisolone sodium succinate (MPSS). ANIMALS: 18 healthy hound-type dogs of both sexes. PROCEDURE: All dogs were given high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, q 6 h for a total of 48 hours) IV. Dogs were assigned randomly to receive concurrent treatment with misoprostol (4 to 6 microg/kg, PO, q 8 h; n = 9) or an empty gelatin capsule (9). Gastroduodenoscopy was performed before and after treatment. Hemorrhage was graded from none (0) to severe (3) for each cardia, fundus, antrum, and duodenum. A total stomach score was calculated as the sum of the regional stomach scores. Food retention was recorded, and pH of gastric fluid was determined. Gastric and fecal occult blood was measured. RESULTS: Gastric hemorrhage was evident in all dogs after MPSS administration, and its severity was similar in both groups. Median total stomach score was 6 for misoprostol-treated dogs and 5.5 for dogs given the gelatin capsule. Difference in gastric acidity, frequency of food retention, and incidence of occult blood in gastric fluid and feces was not apparent between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of misoprostol (4 to 6 microg/kg, PO, q 8 h) does not prevent gastric hemorrhage caused by high doses of MPSS. Alternative prophylactic treatment should be considered.

Evaluation of toxicosis of liposome-encapsulated cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) in clinically normal cats.

OBJECTIVE: To determine adverse effects of single and multiple doses of liposome-encapsulated cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP) administered IV to healthy adult cats. ANIMALS: 10 healthy adult cats. PROCEDURE: 8 cats were given a single dose of L-NDDP (at rates of 75, 100, 150, or 200 mg/m2), and 2 cats were given liposomal lipid (1,500 mg/m2). Six of the 10 cats were given doses of L-NDDP at the maximum tolerated dosage (100 mg/m2) or a lower dosage (75 mg of L-NDDP/m2) at 21-day intervals, for a total of 4 treatments. Hematologic and serum biochemical analyses, urinalyses, and physical examinations were used to monitor effects of L-NDDP. RESULTS: All cats had transient pyrexia, lethargy, vomiting (1 to 3 times/24 h), inappetence, and an acute species-specific infusion reaction that was prevented by administration of atropine-diphenhydramine. Dose-limiting toxicosis was evident as a 10-day course of lethargy, intermittent vomiting, and diarrhea. In cats given multiple doses, dose-related thrombocytopenia, cumulative myelosuppression, transient increased hepatic transaminase activity, and mild to moderate hepatic hydropic degeneration and proximal renal tubular lipidosis in excess of lipidosis expected for this species were detected. Bone marrow hypoplasia was detected in some cats that received higher doses (cumulative dosages of 300 or 400 mg of L-NDDP/m2). CONCLUSION: Cats can safely be given L-NDDP at potentially therapeutic dosages without inducing renal or pulmonary toxicoses. CLINICAL RELEVANCE: Because L-NDDP has better tumoricidal activity than cisplatin (in vivo and in vitro) and is not cross resistant, it may be similarly or more efficacious than cisplatin in humans and dogs.

Adjuvant therapy for melanoma in dogs: results of randomized clinical trials using surgery, liposome-encapsulated muramyl tripeptide, and granulocyte macrophage colony-stimulating factor.

Spontaneous canine oral melanoma (COM) is a highly metastatic cancer, resistant to chemotherapy, and can serve as a model for cancer immunotherapy. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) can activate the tumoricidal activity of the monocyte-macrophage system following i.v. injection. The objective of these studies was to evaluate the therapeutic effectiveness of L-MTP-PE administered alone and combined with recombinant canine granulocyte macrophage colony-stimulating factor (rcGM-CSF) in dogs undergoing surgery for oral melanoma. Ninety-eight dogs with histologically confirmed, clinically staged, oral melanoma were entered into two randomized, double-blind, surgical adjuvant trials. In trial 1, 50 dogs were stratified based on clinical stage and randomized to once a week L-MTP-PE or lipid equivalent (control). When all of the clinical stages were combined, no difference in disease-free survival or in survival time (ST) were detected. However, within stage I, dogs receiving L-MTP-PE had a significant increase in ST compared with control, with 80% of the dogs treated with L-MTP-PE still alive at >2 years. Within each stage II and stage III, there was no difference detected between the treatment groups. In trial 2, 48 dogs were stratified on the basis of clinical stage and extent of surgery (simple resection or radical excision), treated with L-MTP-PE two times a week, and randomized to rcGM-CSF or saline (placebo) given s.c. daily for 9 weeks. Within each stage and when all of the stages were combined, there was no difference between the treatment groups. In both studies, stage I COM is associated with a better prognosis. No effect on survival was observed with regard to tumor location in the oral cavity, sex, type/extent of surgery, or age. In a subset of dogs tested, pulmonary alveolar macrophage cytotoxicity was enhanced with combined rcGM-CSF and L-MTP-PE but not in dogs treated with L-MTP-PE alone. The present study indicates that after surgery, L-MTP-PE administered alone or combined with rcGM-CSF showed no significant antitumor activity in treating advanced stage COM. In early stage COM, L-MTP-PE was shown to result in a prolongation of ST. Furthermore, this study provides additional rationale for the use of the dog model for human malignant melanoma.

Feline bone marrow transplantation: its use in FIV-infected cats.

The use of autologous and allogenic bone marrow transplantations (BMT) in FIV-infected and uninfected cats is a novel therapy for feline hematopoietic diseases and retroviral infections. A total of 13 specific pathogen-free (SPF) cats received either autologous or allogenic BMT and seven of these cats were also infected with FIV before autologous or allogenic BMT. All BMT recipients received total body irradiation of 900 cGy just before BMT. Two FIV-infected and four uninfected cats received autologous uninfected BM cells cryopreserved before BMT. Five infected and two uninfected cats received BM cells from allogenic uninfected donors (RBC-, MHC-, and cross-matched). MHC-matching was based on mixed leucocyte reaction (MLR) and the donor-recipient combination which was compatible by MLR analysis, was used in this study. Recipients were monitored for hematology, immunology, virology, and clinical signs. All FIV-infected and uninfected recipients of autologous BMT had complete engraftment with minimal complications. Uninfected recipients of allogenic BMT had a more severe clinical episode with slower rate of engraftment. None of these BMT groups had mortality. In contrast, only two of the five infected recipients of allogenic BMT survived for a significant period of time (23 and 50 weeks) and rest of the cats succumbed to transfusion reactions. Both infected BMT groups had persistent CD4/CD8 inversion, low CD4+ cell counts, and FIV infection of engrafted peripheral blood mononuclear cells (PBMC). Overall, successful autologous and allogenic BMTs were performed in FIV-free cats. All infected recipients of autologous BMT had compete engraftment and are currently alive, with thelongest survival time being over 1 year. Thus, BMT in combination with antiviral drug therapies may be an alternative therapy against retroviral infection.

Serotonergic neurons differentially modulate the efficacy of two motor neurons innervating the same muscle fibers in Aplysia.

Feeding behavior in Aplysia shows substantial plasticity. An important site for the generation of this plasticity is the modulation of synaptic transmission between motor neurons and the buccal muscles that generate feeding movements. We have been studying this modulation in the anterior portion of intrinsic buccal muscle 3 (I3a), which is innervated by two excitatory motor neurons and identified serotonergic modulatory neurons, the metacerebral cells (MCCs). We have shown previously that serotonin (5-HT) applied selectively to the muscle potently modulates excitatory junction potentials (EJPs) and contractions. All the effects of 5-HT were persistent, lasting many hours after wash out. We examined whether the release of endogenous 5-HT from the MCC could produce effects similar to the application of 5-HT. Stimulation of the MCCs did produce similar short-term effects to the application of 5-HT. MCC stimulation facilitates EJPs, potentiates contractions, and decreases the latency between the onset of a motor neuron burst and the onset of the evoked contraction. The effects of MCC stimulation reached a maximum at quite low firing frequencies, which were in the range of those previously recorded during feeding behavior. The maximal effects were similar to those produced by superfusion with approximately 0.1 microM 5-HT. Although the effects of MCC stimulation on EJPs were persistent, they were less persistent than the effects of 0.1 microM 5-HT. Mechanisms that may account for differences in the persistence between released and superfused 5-HT are discussed. Thus activity in the MCCs has dramatic short-term effects on the behavioral output of motor neurons, increasing the amplitude and relaxation rate of contractions evoked by both B3 and B38 and shifting the temporal relationship between B38 bursts and evoked contractions.

Immunohistochemical detection of p53 tumor suppressor gene protein in canine epithelial colorectal tumors.

Eighty canine epithelial colorectal tumors obtained by excisional biopsy were evaluated immunohistochemically for p53 tumor suppressor gene protein. Dogs in the study average 6.9 years of age (range, 1-12.5 years). A standard avidin-biotin immunohistochemical protocol incorporated a polyclonal antibody of rabbit origin (CM-1) as the primary antibody. Positive staining was observed within all subcategories of lesions, including hyperplastic polyps 1/2 (50%), adenomas 14/29 (48%), carcinomas in situ 9/22 (41%), adenocarcinomas 3/4 (75%), and invasive carcinomas 8/23 (35%). A total of 35/80 (44%) positive tumors wee identified. Fifteen of 31 (48%) benign tumors labeled for p53 protein compared to 20/49 (41%) malignant tumors. Survival data was available for 57/80 (71%) dogs. The average age of dogs within the group with survival data was 4.4 years. Males predominated 34/57 (60%). Mean survival time was 20.6 months. There was no significant difference in survival time between dogs grouped according to p53 immunoreactivity, cellular stain location, or tumor site. A statistically significant increase in survival time was observed between dogs with clean surgical margins and those without (P < 0.018) and for dogs with adenomas or carcinomas in situ over dogs with invasive carcinomas (P < 0.02). In this study, the overall greater positive staining frequency of benign lesions compared to malignant lesions is contrary to data derived from similar immunohistochemical analyses of human tumors and is incongruous with the theorized late-stage participation of the p53 protein in the development of human colorectal cancers. The results of this study suggest that if the p53 tumor suppressor gene protein is involved in the progression of canine colorectal tumors, it may play a relatively early role, possibly analogous to the early appearance of p53 overexpression in precancerous lesions of human ulcerative colitis. Immunohistochemical detection of p53 was not useful prognostically.

Serotonin and the small cardioactive peptides differentially modulate two motor neurons that innervate the same muscle fibers in Aplysia.

The anterior portion of intrinsic buccal muscle 3 (I3a) is innervated by two motor neurons, B3 and B38, which appear to use glutamate as their fast excitatory transmitter. B3 and B38 express the neuropeptides FMRFamide and the small cardioactive peptides (SCPs), respectively. We have shown previously that stimulation of B38 causes release of the SCPs from terminals in the muscle. The I3a muscle also receives input from neurons that use 5HT as a modulatory transmitter. The SCPs and 5HT potently facilitated B38-evoked excitatory junction potentials (EJPs) but had only a small effect on B3-evoked EJPs; however, both the SCPs and 5HT strongly potentiated contractions evoked by both B3 and B38, indicating that the two substances must also act on excitation-contraction coupling. The selective facilitation of B38-evoked EJPs, however, did manifest itself in other parameters. Decreases in the firing frequencies and burst durations that were threshold to evoke contractions and decreases in the latency between the onset of a burst and the onset of the evoked contraction were all much larger for B38 than for B3. Indeed, B38 bursts recorded during feeding-like behavior would be subthreshold for evoking contractions in the absence of this modulation. All of the effects of the SCPs reversed during washout, whereas those of 5HT were persistent, lasting many hours after washout. Thus, the SCPs and 5HT dramatically change the behavioral output of these motor neurons, increasing the amplitude of contractions evoked by both B3 and B38, and shifting the temporal relationship between bursts in B38 and its evoked contractions.